상단 PDF Efficacy of Entecavir in Patients with Hepatitis B virus-Related Decompensated Liver Cirrhosis

I I II I I. . .P P PA A AT T TI I IE E EN N NT T TS S S A A AN N ND D D M M ME E ET T TH H HO O OD D DS S S The study subjects i ncl uded consecuti ve 40 ADV-refractory chroni c hepati ti s B pati ents wi th pri or LAM resi stance.Al l pati ents had LMV resi stance documented by vi rol ogi c breakthrough defi ned as an i ncrease i n thel evelofHBV DNA ofatl east1l og 10 copi es/mL from thel owestpoi nt duri ng therapy , genotypi c anal ysi s of rtM204 sequences,and LAM was swi tched to ADV monotherapy. Pati ents were consi dered to be ADV refractory i f they had al i mi ted vi rol ogi cal response wi th or wi thout documented ADV mutati ons whi l e on ADV.Fourteen pati ents devel oped ADV resi stance and another26 pati ents experi enced subopti malvi rol ogi cal response to ADV monotherapy.These were swi tched to ETV monotherapy from ADV.Pati ents were posi ti ve forHBsAg atl east1 yearbefore LAM therapy. None of the pati ent had co-i nfecti ons(HCV, HIV) or other concomi tantl i verdi seasesuchasal cohol i cl i verdi seaseorautoi mmunel i ver di sease.Al lpati ents had HBV DNA l evel> 5l og 10 copi es/mL before ETV admi ni strati on and recei ved 1. 0mg ETV oncedai l y.Bi ochemi stry and HBV DNA l evel s were tested before and every 3 months duri ng ETV therapy.

Methods: Patients who received allogeneic stem cell transplant were evaluated. Sixty patients, thirty in each group who received LVD or ETV prophylaxis were included in the study. All the baseline and post-transplant data was evaluated which includes anti –CD20 agent exposure, duration of prophylaxis of each drugs and clinical and virological follow up post transplantation. Serum ALT, HBsAg, anti HBs and HBV DNA were the parameters measured.

Peer-review Here the authors report original data on long term efficacy of ADV-based combination therapies, i.e., ADV/ETV and ADV/LMV, on 50 CHB patients with genotypic resistance to ETV. They find higher rates of virological response in patients treated with ADV/ETV vs ADV/LMV and they identify low baseline HBV DNA levels and IVR-3 as independent predictive factor for VR. Although its interest is limited to countries where TDF is not available or not reimbursed, this study will be the largest one on this topic, hence worthy of attention and consideration.

the current guidelines recommended that HBV DNA maintain se- rum HBV DNA level below the detection limit of real-time poly- merase chain reaction as the primary treatment goal. 3,5,9 In the past, a combination of ETV-based regimens had been attempted to treat the CHB patients who had suboptimal response to LAM or LdT/ADV combination therapy. 10,11 However, since the introduc- tion of TDF with strong antiviral efficacy in the treatment of CHB, TDF monotherapy or TDF+other NAs regimens have been at- tempted to treat patients with various drug resistance. 12-16 Berg et al. 12 conducted a prospective randomized controlled trial to compare the antiviral effects of TDF monotherapy and TDF+emtricitabine (FTC) combination therapy in patients with suboptimal responses to ADV. According to the results of their study, complete virologic response (CVR) of TDF monotherapy and TDF+FTC combination therapy groups was 81% and 81%, respectively, at 48 weeks; and there was no difference between the two groups. 12 In a retrospec- tive study of CHB patients with suboptimal response to ADV with or without NAs in LAM-resistant CHB, Cho et al. 13 showed that the CVR of TDF monotherapy group and TDF with NA combina- tion group at 48 weeks was 81.8% and 85.9%, respectively; and

HBeAg seroconversion is considered to be a more reliable marker for durable disease remission than simple loss of HBeAg; however, this is based on minimal evidence and most therapeutic trials have used loss of HBeAg as a therapeutic endpoint. Therefore, HBeAg losses in conjunction with undetectable HBV DNA are reasonable treatment endpoints to measure the efficacy of antiviral treatment, and seroconversion to anti-HBe may not provide further assurance that a virologic response will be sustained (Lok et al, 2001).

In cirrhotic patients, the SVR rate of the genotype non-1 group was similar at around 52.6%. The SVRs of genotype 1 group was reported to be very low at 13-14%, 14,15 however, the SVR was relatively high at 20.8% in this study. This was consistent with the results of relatively high SVRs in Korean patients compared to those in Western countries in studies with patients who did not have liver cirrhosis, but the accurate reason is unknown. 16,17 Furthermore, in this study, even the SVR rate of patients with portal hypertension who showed splenic enlargement in imaging study, thrombocytopenia, or esophageal or gastric varices in upper gastrointestinal endoscopy was 30.0% (9/30), which was better than the results of other studies. There was no significant difference in SVR, compared to patients who did not have portal hypertension. However, the clinical judgment on portal hypertension may be subjective and the number of patients is small in our study. Therefore, accurate diagnosis methods such as measurement of hepatic venous pressure gradient for the assessment of portal hypertension, and studies with a larger number of patients may be needed.

Methods: Two hundred seven adult hepatectomy patients with HCV-related HCC were prospectively identified at our institution be- tween July 2005 and May 2019. Results: One hundred sixteen (56%) hepatectomy patients had HCC in a non-cirrhotic liver. The non-cirrhotic group had better liver function than the cirrhotic group. Consistently, the FIB-4 grade, ALBI grade, and APRI were higher in the cirrhotic group than in the non-cirrhotic group. The cumulative disease-free survival rates and patient survival rates in the non-cirrhotic group were significantly better than in the cirrhotic group. HCC recurrence is related to major liver resection (LR) and alpha-fetoprotein (AFP) > 40 ng/mL, death is related to long hospitalization, and AFP > 40 in multivariate analysis. APRI was the only predisposing factor for HCC recur- rence in non-cirrhotic patients in multivariate analysis. The FIB-4 grade, ALBI grade, and the presence of cirrhosis were not related to HCC recurrence or patient survival in multivariate analyses.

METHODS Patients From January 7, 2007 to December 29, 2015, patients with HBV who underwent LT (both living-donor LT [LDLT] and deceased-donor LT [DDLT]) at Samsung Medical Center (Seoul, Republic of Korea) were included. Primary diseases for transplantation include HCC, liver cirrhosis, and acute liver failure. Data were collected for 3 years after operation. HBsAg positivity, HBV-DNA positivity, and continuous use of TDF or ETV for HBV prevention were included. HCV infection, HIV infection, HDV infection, autoimmune hepatitis, previous renal disease such as IgA nephropathy, focal segmental glomerulosclerosis or other chronic renal failure, and death or re-transplantation within 2 years after operation were exclusion criteria. We defined ‘chronic renal failure’ as ‘e-GFR < 60 mL/

We retrospectively evaluated patients diagnosed with HCV genotype 1b infection who received DCV and ASV combination therapy between August 2015 and March 2017 at five university hospitals in Daegu and Gyeong- sangbuk-do. Exclusion criteria for this study were: pa- tients diagnosed with decompensated cirrhosis, those with hepatocellular carcinoma (HCC) requiring treat- ment, those with a history of liver transplantation, and coinfection with other HCV genotypes, hepatitis B vi- rus, or the human immunodeficiency virus. Decompen- sated cirrhosis was defined as cirrhosis categorized as Child-Turcotte-Pugh class B or C based on the results of blood tests and imaging studies such as abdominal ultrasonography and/or computed tomography. The enrolled patients were divided into three groups: the treatment-naïve, treatment failure (including null re- sponse, partial response, virologic breakthrough, re- lapse after previous treatment), and treatment-intoler- ant group (those who discontinued treatment owing to adverse events). The study protocol was approved by the Institutional Review Board (CR-17-021) of each partici- pating hospital. Patients were not required to provide

Clinical outcomes of living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC) in patients with multiple myeloma (MM) have not been established in terms of HCC recurrence and MM deterioration after LDLT. A 51-year-old man with chronic hepatitis B was diagnosed with HCC and MM. Since the patient also had decompensated liver cirrhosis (LC), he underwent LDLT prior to autologous peripheral blood stem cell transplantation (PBSCT) to prevent fulminant hepatitis due to HBV reactivation. The patient received Epstein-Barr virus prophylaxis and a triple immunosuppressive regimen of tacrolimus, everolimus, and steroid after LDLT. Autologous PBSCT was performed 7 months after LDLT. He showed a complete response to treatment of MM without post-LT complications or HCC recurrence. In conclusion, LDLT could be adapted for treatment of MM patients with combined HCC and decompensated LC because it is an effective strategy of preventing HBV reactivation and HCC recurrence after induction therapy of MM.

hepatitis C and mild to moderate fibrosis including combination regimens of SOF/LDV and SOF plus DCV [10-12,15,16]. In this report, we describe our experience of treating HCV- infected patients before and after liver transplantation in Korea with DAAs. Six patients were treated with DAAs for HCV management before liver transplantation. They bought DAAs directly from abroad. One month after liver transplantation, others received DAAs in the posttransplant period because their liver enzymes and HCV RNA were elevated or their pathologic results showed liver fibrosis related to HCV reactivation. We Table 1. Use of efficacy of direct antiviral agent in the pre-

In conclusion, our study shows that patients can tolerate the administration of ex vivo-expanded allogenic NK cells as adjuvant immunotherapy after curative liver resection, without drug-related adverse events. This study not only establishes the safety and feasibility of producing ex vivo-expanded allogenic NK cells as adjuvant im- munotherapy in patients with HBV-related HCC but may also provide preliminary evidence of efficacy in HCC pa- tients after curative liver resection. Thus, expanded allo- genic NK cells may be expected to produce an appropriate anti-tumor activity. In addition, the long-term safety and cost-effectiveness of adjuvant immunotherapy with ex vivo-expanded allogenic NK cells, which were not ad- dressed in this extended follow-up study, need to be fur- ther evaluated. Further large-scale prospective randomized clinical studies are required to evaluate whether the ex vivo-expanded allogenic NK cells immunotherapy ap- proach provides clinical benefit.

Conclusion TDF was more potent than ETV in the first 3 months after treatment was started, but both had comparable efficacy for long-term treatment. Although the ratio of men and women was positively related with the severity of liver diseases in patients with CHB 25) , we did not observe this tendency in our study. However, a higher proportion of men than that of women had liver cirrhosis or HCC. Patients with CHB and severe liver diseases, especially men, should be carefully mon- itored; furthermore, TDF is more likely than ETV to be an effective option for these patients because TDF tended to decrease the parameters related to HBV infection (e.g., ALT, AST, and HBV DNA level) more rapidly in the first 3 months of treatment compared with ETV.

definitions in various clinical settings, because pattern of prescribing antiviral agent might be quite different depending on the clinical settings. We investigated two different sized hospitals; one is tertiary hospital and the other is secondary hospital. Although we tried to validate the operational definitions using real world data from two different hospitals, we thought 133 patients were not enough to validate for 7166 decompensated patients’ data. Third, the definition of “compensated CHB” is more lenient as it included both CHB and early compensated cirrhosis patients, while “decompensated CHB” is very strict, as it only includes “patients with large amounts of ascites” but generally “ascites is a feature of decompensation.” Patients with moderate ascites who used diuretics and had mild variceal bleeding with no drug therapy were excluded from the study. Consequently, the decompensated complications defined in the present study may have been underestimated compared to those in actual patients with decompensated cirrhosis.

In addition to seroprevalence data, the cost of serologic test- ing, the cost of vaccination, patient compliance, and the like- lihood of the occurrence of a clinically significant fatal HAV superinfection should also be determined to facilitate the iden- tification of the most efficient vaccination strategy. In young or childhood CLD patients, the serum anti-HAV rate is very low and the risk of infection is high, but the symptomatic infection rate and the risk of severe hepatic failure are mini- mal and natural life long immunity is frequently attained after a mild or asymptomatic infection. Therefore, the selec- tive HAV vaccination of middle aged adult CLD patients appears more urgent than the universal vaccination for younger CLD patients (24). Further nationwide large scale studies, including the active evaluation of the clinical significance of acute HAV infection and cost-benefit analyses of different vaccination strategies in different age groups of CLD patients will provide firmer data for designing an optimal vaccination strategy.

similar to or lower than previously reported rates, suggesting no correlation between GZR-containing regimens and HCC inci- dence. 24-29 This analysis had several limitations. Most patients in this study were treatment-naive and HCV mono-infected; caution when ex- trapolating these findings to other patients groups, such as those previously treated for HCV infection or those with HCV/HIV coin- fection. Korean patients in this analysis were identified as individ- uals enrolled at Korean study sites: no additional measures were taken to confirm the nationality/race of patients. The comparison of SVR12 rates between Korean, Asian, and non-Asian patients was restricted to individuals with HCV GT1b infection who re- ceived EBR/GZR for 12 weeks; however, these populations may have differed with regard to other characteristics, such as the proportions with cirrhosis, HIV coinfection, high baseline viral load, or other comorbidities such as chronic kidney disease, inher- ited blood disorders, or active injection drug use.

B virus and hepatitis C virus co-infection: A multicenter observational study Hang-Dong JIA 1,2 , Lei LIANG 1,2 , Chao LI 3 , Han WU 3 , Hong WANG 4 , Ying-Jian LIANG 5 , Ya-Hao ZHOU 6 , Wei-Min GU 7 , Xin-Ping FAN 8 , Wan Yee LAU 9 , Timothy M. PAWLIK 10 , Yong-Kang DIAO 1,2 , Qiu-Ran XU 1,2 , Feng SHEN 3 , Cheng-Wu ZHANG 1 , Dong-Sheng HUANG 1,2 , Tian YANG* ,1,2,3

Twenty-two patients were included in the study. Fifteen (68.2%) were Child’s class B and seven (31.8%) were Child’s class C. Hernia repairs were successful without major complications or recurrence in all patients. Minor complications occurred in only three patients, consisting of two hematomas and one case of scrotal swelling. Complications were resolved sponta- neously without the need for blood transfusion or reintervention. Thirteen patients died during follow-up (59.1%); eight of these patients died within 1 year after hernia repair. However, there was no 30-day postoperative mortality. Five of the eight patients who died were Child’s class B and the remaining three patients were Child’s class C. Deaths were all related to cir- rhotic complications, and there was no operation-related mortality. Conclusion: Inguinal hernia repairs under local anes- thesia in patients with cirrhosis accompanied by ascites were performed safely and effectively. Therefore, surgical repair is recommended even in patients with refractory ascites and poor hepatic function to prevent life-threatening complications or severe pain and improve quality of life.

myocardial infarction, 8,10,23 and peptic ulcer disease 24 in spe- cific hospital settings. Myers, et al. 12 first reported that weekend admission in patients with esophageal variceal hemorrhage was associat- ed only with a small delay in endoscopy and no increase in mortality. Although time to endoscopy and the events of he- patic decompensation were adjusted in that study, 12 Child- Pugh class or MELD score, endoscopic variables, and ini- tial hemodynamic status, all of which have been reported as important prognostic predictors, 1,13,25,26 were not incorporat- ed into the analysis. Additionally, the study may have se- lected for patients with relatively less severe disease by only enrolling those who were admitted via the ER and exclud- ing those who experienced AVH when already hospitalized from other diseases. Accordingly, the results of Myers, et al. 12 should be interpreted cautiously, and we specifically at- tempted to determine the effects of these factors on in-hos- pital mortality in the present study.

patients (4 patients), these findings should be considered with caution. Assessing the severity of liver disease solely by measure- ments of plasma transaminase levels is inadequate. Histologi- cal data are also necessary, possibly with an estimated dura- tion of virus infection. However, due to the lack of histo- logical studies of patient tissues in the current study, we were not able to address this issue. In our study, to enhance cost-effectiveness ALT, AST, and ferritin levels were only measured in the control group. Regardless of whether TTV is a cause of liver disease in thalassemic patients, pathogenic mechanisms of the virus need to be rapidly elucidated in order to develop new strategies to prevent transmission and for therapeutic intervention. Targeted longitudinal studies of TTV in the future will be helpful in this regard [29].