Risk factors for Fontan-associated hepatocellular carcinoma.

AIMS: The incidence of hepatocellular carcinoma (HCC) in patients with Fontan-associated liver disease (i.e., FALD-HCC) has increased over time. However, the risk factors for HCC development remain unclear. Here, we compared the levels of non-invasive markers to the survival rate of FALD-HCC patients. METHODS: From 2003 to 2021, 154 patients (66 men, 42.9%) developed liver disease after undergoing Fontan procedures. HCC was diagnosed in 15 (9.7%) (8 men, 53.3%) at a median age of 34 years (range, 21-45 years). We compared FALD-HCC and non-HCC cases; we generated marker level cutoffs using receiver operating characteristic curves. We sought to identify risk factors for HCC and mortality. RESULTS: The incidence of HCC was 4.9% in FALD patients within 20 years after the Fontan procedure. Compared with non-HCC patients, FALD-HCC patients exhibited higher incidences of polysplenia and esophageal varices. At the time of HCC development, the hyaluronic acid (HA) level (p = 0.04) and the fibrosis-4 index (p = 0.02) were significantly higher in FALD-HCC patients than in non-HCC patients; the total bilirubin (T-BIL) level (p = 0.07) and the model for end-stage liver disease score [excluding the international normalized ratio (MELD-XI)] (p = 0.06) tended to be higher in FALD-HCC patients. Within approximately 20 years of the Fontan procedure, 10 patients died (survival rate, 96.9%). Kaplan-Meier curve analysis indicated that patients with T-BIL levels ≥ 2.2 mg/dL, HA levels ≥ 55.5 ng/mL, and MELD-XI scores ≥ 18.7 were at high risk of HCC, a generally poor prognosis, and both polysplenia and esophageal varices. Multivariate Cox regression analyses indicated that the complication of polysplenia [Hazard ratio (HR): 10.915] and a higher MELD-XI score (HR: 1.148, both p < 0.01) were independent risk factors for FALD-HCC. CONCLUSIONS: The complication of polysplenia and a MELD-XI score may predict HCC development and mortality in FALD patients.

Prevalence of fatty liver disease after liver transplantation and risk factors for recipients and donors.

INTRODUCTION AND OBJECTIVES: Fatty liver disease (FLD) may develop in liver transplant recipients. We investigated the recipient and donor risk factors for FLD development after liver transplantation (LT). METHODS: A total of 108 liver transplant recipients (54 men [50.0%]; median age, 52 [20-68] years) treated from 2011-2020 was enrolled. Three recipients died at < 3 months as a result of infection or blood flow impairment, and were excluded from the long-term FLD study. On evaluation of 88 prospective living donors, fatty liver was observed in 21. The prevalence and risk factors for FLD and survival were evaluated. RESULTS: After LT, 28 of 105 recipients (26.7%) developed FLD. FLD was more common in patients with a high body mass index (BMI) and dyslipidemia (both p < 0.01), primary nonalcoholic steatohepatitis (p = 0.02), after living-donor LT (p = 0.03) and everolimus (EVL) use (p = 0.08). Factors predictive of FLD included EVL use and a high BMI (hazard ratios = 3.00 and 1.34; p = 0.05 and p < 0.01, respectively). Sixteen donors lost 6.5 kg (range: 2.0-16.0 kg) of body weight prior to LT. However, there were no cases of primary non-function, which did not affect the FLD prevalence. Development of FLD did not have a negative impact on LT outcome; the 5-year survival rate was 92.6%. CONCLUSIONS: Recipient factors were more important than donor factors for FLD onset after LT.

Giant Hepatic Hemangioma Causing Prolonged Fever and Indicated for Resection.

Hepatic hemangiomas are benign liver tumors, and most of them progress asymptomatically. We report a case of hepatic hemangioma considered the cause of fever. A 53-year-old woman had a fever of 40°C for about 3 months without infection. Hepatic hemangiomas with internal bleeding of 10 cm in size on liver S8/7 and S3/2 were observed. These were resected laparoscopically for diagnostic treatment. She was afebrile after the operation. The pathological diagnosis was hematoma inside cavernous hemangioma. It should be noted that a bleeding hepatic hemangioma may cause fever of unknown origin and be indicated for resection.

Risk and protective factors of acute kidney injury in decompensated cirrhotic patients with ascites on tolvaptan.

BACKGROUND AND AIM: Acute kidney injury (AKI) is a life-threatening complication of liver cirrhosis. Here, we evaluated the risk factors and characteristics of AKI in cirrhosis. PATIENTS/METHODS: This was a single-center retrospective study. A total of 199 Japanese patients with decompensated liver cirrhosis (104 men, median age 61 years) were enrolled and received tolvaptan orally. Survival rates and new onset of AKI were monitored, and risk factors were evaluated. RESULTS: Forty-six patients (23.1%) suffered an AKI complication and exhibited significantly poorer survival (P < 0.01). The rates of hepatic encephalopathy (P < 0.01) and chronic kidney disease (CKD; P = 0.02) were significantly increased in patients with AKI. The rate of proton pump inhibitor (PPI)/H2 blocker treatment (P = 0.04) was significantly lower, whereas that of ascites drainage was significantly higher in the AKI cases (P < 0.01). The AKI risk was significantly increased in patients with hepatic encephalopathy (HR 4.18, 95% CI 1.618-10.771). In contrast, the incidence of AKI was significantly lower in patients with a higher serum albumin level (HR 0.36, 95% CI 0.142-0.914, P = 0.03). Treatment with PPI/H2 blockers (HR 0.30, 95% CI 0.126-0.711, P < 0.01) or kanamycin/rifaximin (HR 0.26, 95% CI 0.075-0.929, P = 0.04) was significantly associated with a reduced risk of AKI development. CONCLUSIONS: AKI incidence was increased in patients with decreased liver function and was associated with poor survival. PPI/H2 blocker or kanamycin/rifaximin treatment may reduce the risk of AKI.

Long-term outcome of Wilson's disease complicated by liver disease.

BACKGROUND AND AIM: Wilson's disease (WD) is a rare inherited disease that causes systemic copper accumulation. This study examined the long-term course of WD patients with liver disease. METHODS: The 12 patients (9 female patients) enrolled in the study had a median age of 28 years (range: 19-57 years) at their first visit to our hospital. Clinical course and fibrosis markers were assessed in all patients. RESULTS: The median age at diagnosis was 24 years (range: 5-42 years). One patient had acute liver failure (ALF) and 11 patients had chronic liver disease (CLD, 5 with cirrhosis). The patients were followed-up for >20 years. The patient with ALF underwent liver transplantation; the postoperative course during the subsequent 20 years was good. Of the six patients with CLD, liver cirrhosis developed in four patients with interrupted chelating therapy. Two of the patients with cirrhosis died; one of these two patients died at 21 years after liver transplantation. However, the remaining patients with continued treatment exhibited a favorable clinical course for 30 years and none developed hepatocellular carcinoma (HCC). The duration of chelation therapy was significantly negatively correlated (P < 0.05) with the fibrosis-4 index or aspartate aminotransferase to platelet ratio index (APRI) score at the last visit; lower values were indicative of greater treatment success. Patients with an APRI score ≥1.5 had a significantly worse prognosis (P < 0.05). CONCLUSION: Long-term survival of patients with WD was achieved without worsened liver function or carcinogenesis with appropriate treatment. Treatment disruption should be avoided.

The utility of liver transplantation to treat acute liver failure caused by adult-onset Still's disease: case reports.

PURPOSE: Adult-onset Still's disease (AOSD) is an inflammatory condition commonly complicated by mild liver dysfunction. However, severe liver failure is rarely reported. We report three cases of severe acute hepatic failure (ALF) associated with AOSD. We encountered three cases of acute liver failure (ALF) with encephalopathy. RESULTS: Case 1 was a 75-year-old female, who was started on a steroid (prednisolone, PSL) to treat AOSD; this was gradually tapered. Two months later, severe ALF developed. She died despite an increase in the PSL dose and artificial liver support. Case 2 was a 26-year-old-female taking PSL 30 mg/day to treat subacute thyroiditis. PSL was tapered, and she received methyl PSL pulse therapy and artificial liver support, but this did not cure the ALF. Liver transplantation (LT) was performed 25 days later. Three years later, the same symptoms were observed and we diagnosed AOSD. Case 3 was a 56-year-old-female who met the AOSD criteria. PSL 50 mg/day was started and then tapered. Methyl PSL pulse therapy was prescribed to treat hemophagocytic syndrome, but she required LT on hospital day 13. CONCLUSION: In AOSD cases, ALF is rarely complicated; urgent LT should be considered only for patients with AOSD-related severe ALF.

Hereditary Apolipoprotein A-1 Amyloidosis With Glu34Lys Mutation Treated by Liver Transplantation: A Case Report.

Hereditary apolipoprotein A-1 (ApoA-1) amyloidosis is a rare disease characterized by progressive deposition of amyloid fibrils in the kidney, heart, and liver. We observed a 45-year-old male patient with liver failure. Liver dysfunction was detected at 30 years of age during an annual health check-up. At 35 years of age, renal dysfunction was also found. At 40 years of age, the pathologic findings of the liver revealed amyloid deposition. A testis biopsy specimen taken at 42 years of age to identify the cause of male infertility showed amyloid accumulation. At 43 years of age, the amyloid results and genetic profile led to a definitive diagnosis of hereditary ApoA-1 amyloidosis caused by Glu34Lys mutation. A family history was absent. Liver failure showed Budd-Chiari-like formation, including enlargement of the caudate lobe and liver congestion. Although the patient showed end-stage liver cirrhosis and renal failure, only liver transplant was performed considering the burden for a living donor. The enlarged liver (4.9 kg) showed amyloid deposition in parenchyma and the space of Disse. Amyloid also accumulated in the giant spleen. The APOA1 mutation Glu34Lys is extremely rare, and in this case hepatic failure was successfully treated by liver transplant to both replace organ function and reduce production of the amyloidogenic ApoA-1-variant protein. Careful observation for reaccumulation of amyloidosis in the organ is required.

Development and course of diabetes according to genetic factors and diabetes treatment among patients with nonalcoholic fatty liver disease.

OBJECTIVES: Many patients with nonalcoholic fatty liver disease (NAFLD) also have diabetes. However, the genetic factors associated with diabetes in NAFLD are unclear. In this study, we investigated the clinical course and risk factors of diabetes development. METHODS: A total of 544 patients (275 men; 50.6%) with a median age of 53 y and biopsy-confirmed NAFLD enrolled in the study. Patatin-like phospholipase 3 and voltage-gated potassium channel KQT-like subfamily member 1 (KCNQ1) single nucleotide polymorphisms were identified in 287 cases. There were 272 patients without diabetes, and 64, 141, and 67 patients with diabetes not treated with an oral hypoglycemic agent, treated with an oral hypoglycemic agent, and treated with insulin, respectively. Changes in biochemical parameters and body weight over a 1-y period were determined in patients treated with incretin agents (n = 91), a sodium glucose cotransporter 2 inhibitor (n = 19), or both (n = 33). The prevalence and risk factors for diabetes development among patients with NAFLD were determined in nondiabetic patients. RESULTS: Among patients with NAFLD, half of the patients had diabetes and the incidence was high in those with advanced fibrosis. Reduction in body weight was higher after sodium glucose cotransporter 2 inhibitor treatment (P = .050) and in KCNQ1 CC genotype patients (P < .05). Reduction in hemoglobin A1c level was significantly lower in patatin-like phospholipase 3 GG subjects (P < .05). De novo diabetes developed in 44 patients (10-y incidence: 17.9%), especially in obese (P = .046) and KCNQ1 CC genotype patients (P < .01). CONCLUSIONS: Patient genetic background affected treatment response and incidence of diabetes in patients with NAFLD.

Outcomes of Japanese patients with non-alcoholic fatty liver disease according to genetic background and lifestyle-related diseases.

INTRODUCTION AND OBJECTIVES: Genetic background may be involved in the mechanisms of liver injury and the development of non-alcoholic fatty liver disease (NAFLD). However, its contributions to the long-term outcome of NAFLD have been unclear. METHODS: We enrolled 314 Japanese patients with biopsy-confirmed NAFLD from 2000 to 2018 (161 men [51.3%]; median age, 53 [14-84] years; 114 with advanced fibrosis [37.5%]) in the patients without hepatocellular carcinoma at diagnosis. Genomic DNA was extracted from peripheral blood and single nucleotide polymorphisms (SNPs) were analyzed. Associations of mortality with patatin-like phospholipase 3 (PNPLA3) and aldehyde dehydrogenase 2 (ALDH2) were analyzed. Finally, a subgroup analysis according to lifestyle-related disease was performed. RESULTS: During the median 7 years of follow-up, 20 patients (6.4%) died (13 liver-related [4.1%] and 7 non-liver-related deaths [2.2%]). Patients with ALDH2 (non-GG genotype) who had reduced alcohol metabolism tended to have a poor prognosis (p = 0.06). Patients carrying both risk SNPs of PNPLA3 (GG) and ALDH2 (non-GG) had a significantly poor prognosis (p = 0.01). In the subgroup analysis, patients with PNPLA3 (GG) who were non-diabetics (p = 0.06) or non-dyslipidemic (p = 0.03), with ALDH2 (non-GG) who were non-dyslipidemic (p = 0.01) or hypertensive (p = 0.03), also had a poor prognosis. The Cox analysis revealed that ALDH2 (non-GG) was associated with a poor prognosis (Hazard ratio: 4.568, 95% Confidence Interval: 1.294-16.131, p = 0.02) similar to the liver function tests. CONCLUSIONS: Genetic background may affect NAFLD prognosis and ALDH2 SNP could predict the outcome.

A case of hemorrhage of hepatocellular carcinoma resembling a hepatic cyst arising from non-cirrhotic steatohepatitis.

A 70-year-old female was found to have multiple hepatic cysts at her annual checkup. In the posterior segment of the right lobe of the liver, an 81 × 67 mm circular cystic lesion was detected by contrast-enhanced computed tomography (CT). Magnetic resonance imaging (MRI) of the cyst revealed a solid component. The cyst had a capsule-like structure and non-uniform fluid accumulation suggested bleeding. Since the lesion was enlarged and malignancy could not be ruled out, it was surgically resected. Histopathologically, reticular fibers of the liver were seen in necrotic tissue and the lesion was diagnosed as a bleeding hepatocellular carcinoma (HCC). The non-cancerous liver tissue showed non-cirrhotic steatohepatitis. This was an unusual presentation of HCC.

Bardet-Biedl Syndrome Caused by Skipping of SCLT1 Complicated by Microvesicular Steatohepatitis.

We treated the case of a 22-year-old male patient with liver dysfunction. At 1 year of age, hepatic fibrosis was suspected. In addition, due to the presence of retinitis pigmentosa, renal failure, obesity, mental retardation, and hypogonadism, he was diagnosed with Bardet-Biedl syndrome (BBS). Skipping of exons 14 and 17 in the sodium channel and clathrin linker 1 (SCLT1) gene was observed. At 22 years of age, the liver enzyme levels were further elevated and a diagnosis of microvesicular steatohepatitis was made. Insulin resistance, a reduction of muscle mass, an impairment of the fatty acid metabolism, and hyperleptinemia in this syndrome may cause steatohepatitis.

Characteristics of NAFLD Based on Hypopituitarism.

Background: Hypopituitarism and hypothalamic disorders, which induce central obesity and appetite disorder, are associated with nonalcoholic fatty liver disease (NAFLD). We retrospectively analyzed the clinical features of NAFLD patients with hypopituitarism. Patients. We examined the cases of 15 NAFLD patients with hypopituitarism (mean age, 39.4 years; males/females, 11/4). The causes of hypopituitarism were surgical in eight cases (six with craniopharyngioma and two with prolactinoma) and nonsurgical in seven cases, including unexplained hypopituitarism in five cases, Sheehan syndrome in one case, and one case that occurred after the radiation therapy. Serum adiponectin, soluble tumor necrosis factor receptor-2 (TNFR-2), and leptin levels were measured. Results: We compared the cases of the eight patients who underwent cranial surgery due to craniopharyngioma or prolactinoma and seven nonsurgical cases. The body mass index (surgery group, 30.2 ± 4.1; nonsurgery group, 29.2 ± 14.2) and the rate of diabetes (75% in surgery group, 14.3% in nonsurgery group) tended to be higher in the surgery group, and the hepatic fibrosis grade (surgery group, 3.75 ± 0.38; nonsurgery group, 1.64 ± 1.07) was significantly higher in the surgery group. The levels of adipocytokines, serum adiponectin, and serum soluble TNFR-2 showed no correlation with hepatic fibrosis, whereas the serum leptin levels were significantly correlated with liver fibrosis (R = 0.696). Conclusion: The hepatic fibrosis grade rapidly progressed in the cranial surgery cases of NAFLD patients with hypopituitarism, possibly in association with BMI, diabetes mellitus, and leptin. In such cranial surgery patients, strong interventions should be considered from the early stage, including diet education, hormone replacement, and more.

Characteristics of hepatocellular carcinoma arising from Fontan-associated liver disease.

AIM: Hepatocellular carcinoma (HCC) can arise from Fontan-associated liver disease (FALD); this is known as FALD-HCC. The clinical features of FALD-HCC are unclear. Thus, we examined the incidence and clinical characteristics of FALD-HCC. METHODS: From 1972 to 2019, 122 patients developed liver disease after undergoing Fontan procedures. HCC was diagnosed in 12 (9.8%) FALD patients. We compared FALD-HCC and non-HCC patients. RESULTS: The incidence of HCC was 0.8% and 2.9% in FALD 10 and 20 years after the Fontan procedure, respectively. The median age of patients at diagnosis of HCC was 32.5 years (range 20.6-46.1 years), and seven of the 12 patients were men. Patients with FALD-HCC had a higher incidence of liver cirrhosis and polysplenia than non-HCC patients. Liver tumors were detected as single nodules in eight patients, and the median diameter was 47 mm (range 11-105 mm). HCC was treated by surgical resection in two patients, transcatheter arterial chemoembolization or chemotherapy in three patients, and proton beam therapy in four patients. Three patients could not be treated because of their poor condition. Four patients died of liver/cardiac failure and HCC, and HCC was controlled in three patients. The survival rate after 25 years was significantly lower in patients with FALD-HCC than non-HCC patients (68.6% vs. 97.9%, respectively; P < 0.01). CONCLUSIONS: Of the 122 patients with FALD, 12 developed HCC 20 years after surgery. Because complications of HCC are associated with poor prognosis, constant surveillance for HCC should begin 10 years after surgery.

Long-term outcomes of non-alcoholic fatty liver disease and the risk factors for mortality and hepatocellular carcinoma in a Japanese population.

BACKGROUND AND AIM: The incidence of mortality and hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease (NAFLD) has been reported, but the long-term outcomes of Japanese patients with NAFLD are not fully evaluated. METHODS: We enrolled 365 Japanese patients with biopsy-confirmed NAFLD (1990-2008) followed for ≥ 6 months: 185 males (50.7%); median age (54 years); advanced fibrosis 108 (29.8%); HCC, n = 26 (7.1%); diabetes, n = 191 (52.3%); dyslipidemia, n = 234 (64.1%); and hypertension, n = 193 (52.9%). We analyzed the survival and new-onset HCC rates for hepatic fibrosis as well as complications and the treatment of lifestyle-related diseases. RESULTS: During the median 7.1-year follow-up, 44 patients (12.1%) died: n = 28 liver-related (10 years liver-related death, 9.4%) and n = 16 non-liver-related deaths (10 years non-liver-related death, 4.9%). Both incidence rates were significantly higher in the advanced fibrosis group. The incidence of HCC at 10 years was 20.1% in the advanced fibrosis group, and the mortality was increased in patients with higher age, history of HCC, lower seru\m level of albumin, higher level of γ-glutamyltransferase, and insulin treatment for diabetes. Risk factors for HCC onset were higher levels of aspartate aminotransferase and triglyceride and hypertension treatment. Platelet count < 11.5 × 104 /µL was revealed as a risk factor for death and HCC development. CONCLUSIONS: The rates of both liver-related and non-liver-related deaths and HCC development were significantly prominent in the patients with advanced fibrosis. It is important to identify and treat NAFLD patients who have several risk factors and advanced fibrosis, which might be predicable simply by the platelet count.

A case of Fontan-related hepatocellular carcinoma successfully treated with proton beam therapy.

A 27-year-old woman was admitted to our hospital due to a liver tumor. She had been born late at 41 weeks of gestation and had heterotaxy syndrome, polysplenia, and complete transposition of the great arteries. She underwent percutaneous balloon angioplasty at 5 years of age and the Fontan procedure at 6 years of age. At 25 years of age, computed tomography detected liver congestion. Her alpha-fetoprotein level increased from 13 to 2098 ng/dL (L3 fraction 1.8%) at 27 years of age. Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid enhanced magnetic resonance imaging showed a 22-mm liver tumor in the second liver segment. The liver tumor was enhanced in the arterial phase and washed-out in the hepatobiliary phase; the patient was, therefore, diagnosed with hepatocellular carcinoma. Radiofrequency ablation and surgery were not indicated due to the proximity of the tumor to the inferior vena cava. Therefore, proton beam therapy was selected as conservative therapy, and a dose of 74 Gray equivalents in 37 fractions was administered at the University of Tsukuba Hospital. There were no severe adverse events and she survived for 38 months after treatment without recurrence.

Characteristics of acute hepatitis A virus infection before and after 2001: A hospital-based study in Tokyo, Japan.

BACKGROUND AND AIM: The incidence of acute hepatitis A [AH (A)] is decreasing because of improvements in hygiene; however, cases of sporadic severe hepatitis are still being reported. We assessed the epidemiology of AH (A) in Japan. METHODS: This was a hospital-based retrospective study, in which 126 AH (A) patients (96 men [76%], median age 39 [range, 19-66] years) were enrolled. Patients diagnosed with AH (A) before 2001 (n = 79) and after 2001 (n = 47) were compared. RESULTS: The incidence of AH (A) showed peaks in 1990, 1999, and 2018. After 2001, one patient had hepatitis B virus, four had human immunodeficiency virus, and three had syphilis coinfections. Before and after 2001, HAV was transmitted, respectively, by raw oysters (28% and 26%), overseas travel (19% and 28%), and sexual contact (0% and 19%) (P < 0.01). The frequencies of symptoms were appetite loss (51% and 32%), fever (63% and 81%), and diarrhea (3% and 13%) (all P < 0.05), respectively. On admission, the median levels of alanine aminotransferase (1455 and 3069 U/L) and γ-glutamyl transpeptidase (221 and 345 U/L) were significantly higher (P < 0.01), and the prothrombin time (77.5% and 65.9%) and platelet count (22.7 and 16.4 × 10/µL) were significantly lower after 2001 (P < 0.05). A time to normalization of the bilirubin level ≥ 30 days was associated with older age and a diagnosis of AH (A) after 2001. CONCLUSIONS: Outbreaks and severe AH (A) cases due to sexual transmission have been reported recently. It is necessary to examine their sexual behavior and other sexual infection.

Hepatocellular carcinoma after direct-acting antiviral drug treatment in patients with hepatitis C virus.

BACKGROUND AND AIM: Given the use of direct-acting antivirals (DAAs) to treat hepatitis C virus (HCV), their effects on hepatocarcinogenesis should be determined. METHODS: This study enrolled 349 patients with HCV who underwent DAA treatment at our hospital between 2014 and 2018. Their median age was 65 years, and 184 were male; 301 cases were of HCV serotype 1, and 48 were of serotype 2. The DAA treatment was daclatasvir/asunaprevir in 107 cases, sofosbuvir (SOF)/ledipasvir in 147 cases, ritonavir-boosted ombitasvir/paritaprevir in 28 cases, elbasvir/grazoprevir in 19 cases, and SOF/ribavirin in 48 cases. The patients' histories included hepatocellular carcinoma (HCC) in 45 cases, liver transplant (LT) in 10 cases, and kidney transplant (KT) in 17 cases. RESULTS: Sustained virological responses occurred in 335 cases (96%). DAA treatment was initiated a median of 16.3 months after HCC treatment. After DAA treatment, 15 cases (33%) had recurrence of HCC after a median of 11.6 months, and 3 cases (1%) developed de novo HCC. Six LT patients and one KT patient had HCC; however, no HCC was observed after DAA. The incidence of HCC was significantly higher in patients with multiple HCC treatments in the Cox hazard model (hazard ratio 1.664, 95% confidence interval 1.134-2.441, P < 0.01). Surgical resection or LT reduced the risk of HCC. CONCLUSIONS: DAA did not increase the rate of HCC, even in immunosuppressed patients. However, careful follow-up for HCC recurrence is required in previously treated cases.

Impact of continued administration of tolvaptan on cirrhotic patients with ascites.

BACKGROUND: The vasopressin V2-receptor antagonist tolvaptan is used to treat cirrhotic patients with ascites. We investigated the outcome of long-term treatment. METHODS: This was a single-center retrospective study. Overall, 170 cirrhotic patients (95 males, median age 63 years) were enrolled and received tolvaptan orally after hospitalization for ascites, which included treatment with conventional diuretics. We compared patients who withdrew tolvaptan treatment after < 1 year (n = 90) with patients who continued treatment for ≥1 year (n = 37). In continuously treated patients, the pretreatment and post-treatment (1 year) blood biochemistry values were assessed. RESULTS: Overall, 37 patients received treatment for ≥1 year and showed a higher response after tolvaptan therapy. The reduction in body weight was 2.0 (- 3.4-17.2) kg compared to discontinued cases, which had a body weight reduction of 1.1 (- 6.2-7.5) kg after 1 week. The group that received treatment for ≥1 year had a significantly lower rate of the complication gastroesophageal varices and also showed better liver function. In patients with continued treatment, serum levels of albumin was significantly higher without renal disturbance after 1 year of treatment. The prothrombin time/international normalized ratio and ammonia level were also significantly improved. Multivariate analyses showed that a change in body weight reduction and serum levels of albumin were predictive factors of continued administration. CONCLUSIONS: Long-term tolvaptan treatment increased serum levels of albumin, decreased ammonia levels, and preserved renal function after 1 year of treatment. A reduction in body weight after 1 week was associated with a favorable outcome of tolvaptan therapy.

Elevated α-Fetoprotein in the Absence of Carcinoma Caused by Relapse of Hepatitis C Viral Infection after Liver Transplantation.

We report a rare case of marked elevation of α-fetoprotein in the absence of hepatocellular carcinoma caused by a relapse of hepatitis C virus (HCV) infection. A 58-year-old man underwent liver transplantation to treat hepatocellular carcinoma caused by HCV-related liver cirrhosis. The HCV was of genotype 2a, and the ribonucleic acid titer was >8.0 log IU/mL. Direct-acting antiviral drugs were prescribed for 12 weeks; however, the HCV infection relapsed after treatment had ended, and α-fetoprotein levels increased to 8,981 ng/mL. Imaging did not reveal any malignancies. The patient initiated interferon therapy, at which time AFP levels decreased, and the HCV was successfully cleared.