Clinical Outcomes of Next-Generation Microwave Thermosphere Ablation for Hepatocellular Carcinoma with Primarily Hepatitis-Related Etiology.

BACKGROUND AND AIM: We investigated the clinical outcomes of patients with hepatocellular carcinoma (HCC) who underwent next-generation microwave thermosphere ablation (MTA). METHODS: A total of 429 patients with 607 HCCs (maximum tumor diameter ≤40 mm) were included. We defined the following areas of the liver as those where MTA therapy is difficult to perform: caudate lobe and areas near the primary and secondary branches of the intrahepatic portal vein, inferior vena cava, gallbladder, heart, duodenum, abdominal esophagus, collateral veins around the liver, and spleen. Factors which predisposed patients to local tumor recurrence in the context of tumor location and complications were examined. RESULTS: The primary etiologies of HCC were hepatitis-related: 259 (60.4%) cases of HCV, 31 (7.3%) cases of HBV, and two instances of both. Median maximum tumor diameter was 15.0 (interquartile range, 10.0-21.0) mm. There were 86 tumors in areas of the liver where MTA is difficult. The most common area was near the primary and secondary branches of the intrahepatic portal vein (26 nodules). The cumulative local tumor recurrence rates at 1, 2, and 3 years were 4.4%, 8.0%, and 8.5%, respectively. The cumulative local tumor recurrence rate differed significantly by tumor size group: 6.6%, 13.8%, and 29.4% at three years in the ≤20 mm group (n = 483), 20-30 mm group (n = 107), and ≥30 mm group (n = 17), respectively (p < 0.001). The cumulative local tumor recurrence rate was similar despite difficult-to-treat status (p = 0.169). In the multivariable analysis, tumor size (>15 mm) (hazard ratio [HR], 2.15; 95% confidence interval [CI], 1.11-4.16; p = 0.023) and ablative margin (<3 mm) (HR, 2.94; 95% CI, 1.52-5.71; p = 0.001) were significantly associated with local tumor recurrence. Only tumor size (>15 mm) (odds ratio, 3.41 95% CI, 1.53-7.84; p = 0.026) was significantly associated with complications. CONCLUSIONS: MTA is a safe and effective local ablation therapy for HCC, even for tumors located in areas of the liver where local ablation therapy is difficult.

[Cirrhotic cardiomyopathy-associated acute cardiac failure in a patient with decompensated alcoholic cirrhosis with massive hepatic hydrothorax].

Cirrhotic cardiomyopathy (CCM) is a chronic cardiac dysfunction in patients with cirrhosis and is characterized by altered diastolic relaxation, blunted contractile response to stress, and electrophysiological abnormalities;however, causes of CCM are unknown. Moreover, reduced cardiac afterload due to cirrhosis-related vasodilatation often masks cardiac insufficiency, whereas rapid hemodynamic overload reveals the presence of cirrhotic cardiomyopathy. Herein, we present the case of previously unrecognized cirrhotic cardiomyopathy that became overt with the development of severe acute cardiac failure. The rapidly worsening hepatic hydrothorax increased cardiac preload and intrathoracic pressure, which impaired cardiac filling. Furthermore, cardiac contractile function might have been worsened by hypoxia due to passive atelectasis and concomitant anemia.

Hepatocellular Carcinoma in a Patient with Hereditary Hemorrhagic Telangiectasia.

A 76-year-old woman with hereditary hemorrhagic telangiectasia (HHT) showed elevated serum hepatobiliary enzyme levels, and abdominal imaging studies revealed a hepatic tumor. Her serum alpha-fetoprotein level was 759.5 ng/mL. A pathological examination after hepatectomy confirmed a diagnosis of hepatocellular carcinoma (HCC). An examination of the surrounding liver revealed dilated vessels and thickened endothelial cells without inflammations. HHT patients without other risk factors (like this patient) reportedly have a lower incidence of common cancers, including HCC, in comparison to the unaffected population. One intriguing hypothesis that might explain the hepatocarcinogenesis in this situation is the ischemic liver cirrhosis theory, which suggests that chronic ischemia may cause parenchymal strain and promote inappropriate hepatocyte proliferation.

Infectious Hepatic Cyst: An Underestimated Complication.

Objective An infectious hepatic cyst (IHC) is a hepatic cyst complicated with secondary infection and is generally assumed to be rare. However, we have experienced no small number of patients with IHC in recent clinical practice. We therefore examined the incidence and clinical characteristics of IHC. Methods The medical records of patients with IHC who were hospitalized at our institution between January 2012 and December 2016 were retrospectively reviewed. Their demographic factors, biochemical, bacteriological, imaging, and treatment results were explored and compared with those of patients with pyogenic liver abscess (PLA). Patients Twelve patients with IHC and 39 with PLA were identified. Results The IHCs were significantly larger in diameters than the PLAs, and patients with IHCs tended to be older and more often women than those with PLAs. IHCs showed characteristic imaging features, including heterogeneous contents with occasional fluid-debris levels, a thickened cystic wall with rim enhancement, perilesional edema and hyperaemia. Patients with IHCs had a significantly shorter hospital stay than those with PLAs. Conclusion Physicians should note that IHCs are not rare. A careful imaging evaluation can suggest an IHC, and the timely aspiration of the content can lead to an accurate diagnosis. The cystic wall may keep the infectious material confined within the IHC, resulting in the observed good treatment outcome with catheter drainage.

Increasing incidence of elderly-onset autoimmune hepatitis.

AIM: Autoimmune hepatitis (AIH) commonly shows bimodal distribution of onset age: at young adulthood and at 50-60 years-of-age. However, in recent times, the incidence of elderly-onset AIH seems to be increasing. This study aimed to investigate whether the incidence of elderly-onset AIH is increasing, and whether these patients show any clinical features different from those observed in younger patients. METHODS: Data about patients with newly diagnosed AIH visiting the Japanese Red Cross Society Himeji Hospital, Himeji, Hyogo, Japan, were retrospectively collected for the period ranging from January 2010 to May 2016. A total of 71 patients (56 women and 15 men, age 18-88 years) were included in this study. Patients were divided into two cohorts: elderly (≥70 years; n = 28) and adult cohort (15-69 years; n = 43). Demographic and clinical characteristics, biochemical and serological markers, radiological and histological findings, and therapeutic courses were evaluated. RESULTS: The median age of the patients was 65 years, the most frequent range being the 70s (37%), followed by the 60s (25%). The elderly cohort had significantly higher levels of serum immunoglobulin G and antinuclear antibody, lesser hepatitis activity scores, and lesser chance of developing other autoimmune diseases. They tended to have higher C-reactive protein levels and lower serum alanine aminotransferase levels. All patients achieved clinical remission after treatment. CONCLUSIONS: This study clearly showed an increase in the incidence of elderly-onset AIH. These patients had some unique characteristics, showing that the development of elderly-onset AIH is influenced by age-associated immune dysfunction called immunosenescence. Geriatr Gerontol Int 2017; 17: 1722-1728.

Synergistic anti-tumor effects of zoledronic acid and radiotherapy against metastatic hepatocellular carcinoma.

A 72-year-old man with advanced hepatocellular carcinoma and decompensated hepatitis C virus-related cirrhosis suffered from a metastatic femoral fracture. After undergoing radiotherapy, he was only treated with supportive care, except for the administration of zoledronic acid (ZA). Thereafter, the initially elevated serum α-fetoprotein and des-gamma carboxyprothrombin levels declined to within the normal ranges. Hepatic and metastatic adrenal tumors, distant from the radiation field, exhibited a surprising regression. ZA is known to inhibit the activity of osteoclasts, bone-residential macrophages, and has been reported to have a direct anti-tumor effect. ZA may adjust the immunological milieu in tumor microenvironments by inhibiting the tumor-associated macrophages. Because radiotherapy can enhance the presentation of tumor-associated antigens, ZA and radiotherapy may exert synergistic anti-tumor effects.

Indices of initial hepatitis C virus RNA reduction rate to predict efficacy of interferon-beta followed by peginterferon plus ribavirin for genotype 1b high viral load.

AIM: Initial hepatitis C virus (HCV) RNA reduction was investigated as a potential index for sustained virological response (SVR) in the treatment of interferon (IFN)-ß followed by peginterferon plus ribavirin (PEG IFN/RBV). METHODS: The treatment course was retrospectively analyzed in 64 genotype 1b patients with a HCV RNA level of 5.0 logIU/mL or higher. IFN-ß was administrated twice a day for 2 weeks followed by 24 or 48 weeks of PEG IFN/RBV. The serum HCV RNA level was measured by real-time polymerase chain reaction before administration and at 1, 2 and 4 weeks of therapy. RESULTS: By the duration of PEG IFN administration, the SVR rates were 11% (2/18, <19 weeks), 64% (23/36, 20-24 weeks) and 40% (4/10, 25-72 weeks) (P = 0.0011, χ(2) -test). The SVR rate was high in patients in whom the HCV RNA level had decreased by 2.5 logIU/mL or greater at 1 week of IFN-ß (29/55 [53%] vs 0/9 [0%], P = 0.0029, χ(2) -test). Among these patients, the SVR rate was even higher in those with continuous reduction in the first 2 weeks after the switch to PEG IFN/RBV (27/45 [60%] vs 2/10 [20%], P = 0.0048). Age below 65 years, no previous IFN course and good initial HCV RNA reduction were significantly associated with SVR on multivariate analysis, and the SVR rate was 95% (18/19) among these patients. CONCLUSION: The 2.5 logIU/mL reduction in HCV RNA at 1 week of IFN-ß and the continuous reduction just after the switch to PEG IFN/RBV are important SVR-predictive indices.

Mesenteric panniculitis presenting as liver dysfunction.

Mesenteric panniculitis is a non-specific inflammatory disorder affecting adipose tissues of the mesentery. Mesenteric adipose tissues contain macrophages and other inflammatory cells, which may secrete tumor necrosis factor α, interleukin (IL)-1, and IL-6. These cytokines collect into the portal vein and thereby flow into the liver, possibly influencing hepatic function. Mesenteric panniculitis often occurs with inflammatory reactions such as fever and elevated erythrocyte sedimentation rates. Systemic inflammatory disorders can evoke acute cholestatic liver involvement, which is mediated by proinflammatory cytokines. However, no reports have focused on the association between mesenteric panniculitis and liver involvement. We report a rare case of mesenteric panniculitis presenting as liver dysfunction. Immunohistochemical staining of the liver demonstrated a marked decrease in expression of canalicular transport systems. These findings indicated cholestatic liver dysfunction associated with mesenteric panniculitis.

Successful hepatectomy for intraperitoneal rupture of pyogenic liver abscess caused by Klebsiella pneumoniae.

Klebsiella pneumoniae (KP) is the most common cause of pyogenic liver abscess in eastern Asia. KP liver abscess commonly presents as a single large abscess with a predominantly solid consistency. It is sometimes unsuitable for percutaneous catheter drainage because of the poorly liquefied contents. Antibiotic therapy alone may raise a probability of treatment failure and occurrence of complications such as abscess rupture. Hepatic or portal venous thrombosis, hematogenous spread, and spontaneous rupture also occur frequently. We report a case of KP liver abscess with a typical solid appearance, complicated by disseminated intravascular coagulation, spontaneous rupture, and pyogenic spondylitis.

Twenty four-week peginterferon plus ribavirin after interferon-ß induction for genotype 1b chronic hepatitis C.

AIM: To investigate the possibility of shortening the duration of peginterferon (Peg-IFN) plus ribavirin (RBV) combination therapy by incorporating interferon-ß (IFN-ß) induction therapy. METHODS: A one treatment arm, cohort prospective study was conducted on seventy one patients. The patients were Japanese adults with genotype 1b chronic hepatitis C, HCV-RNA levels of ≥ 5.0 Log IU/mL or 100 KIU/mL, and platelet counts of ≥ 90 000/µL. The treatment regimen consisted of a 2 wk course of twice-daily administration of IFN-ß followed by 24 wk Peg-IFN plus RBV combination therapy. We prolonged the duration of the Peg-IFN plus RBV therapy to 48 wk if the patient requested it. RESULTS: The patients, including 44% males, were characterized by an median age of 63 years (range: 32-78 years), an median platelet count of 13.9 (range: 9.1-30.6) × 10(4)/µL, 62% IFN-naïve, and median HCV-RNA of 6.1 (range: 5.1-7.2) Log IU/mL. The sustained virologic response (SVR) rates were 34% (Peg-IFN: 1-24 wk, n = 61, 95% confidence interval (CI): 24%-47%) and 55% (Peg-IFN: 20-24 wk, n = 31, 95% CI: 38%-71%, P < 0.001; vs Peg-IFN: 1-19 wk). The SVR rate when the administration was discontinued early was 13% (Peg-IFN: 1-19 wk, n = 30, 95% CI: 5%-30%), and that when the administration was prolonged was 50% (Peg-IFN: 25-48 wk, n = 10, 95% CI: 24%-76%, P < 0.05; vs Peg-IFN: 1-19 wk). In the patients who received 20-24 wk of Peg-IFN plus RBV, only the higher platelet count (≥ 130 000/µL) was significantly correlated with the SVR (odds ratio: 11.680, 95% CI: 2.3064-79.474, P = 0.0024). In 45% (14/31) of the patients with a higher platelet count (≥ 130 000/µL) before therapy, the HCV-RNA level decreased to below 3.3 Log IU/mL at the completion of IFN-ß, and their SVR rate was 93% (13/14) after 20-24 wk administration of Peg-IFN plus RBV. CONCLUSION: These results suggest the possibilities of shortening the duration of Peg-IFN plus RBV combination therapy by actively reducing HCV-RNA levels using the IFN-ß induction regimen.

Short-term intravenous interferon therapy for chronic hepatitis B.

AIM: To investigate the therapeutic efficacy of short-term, multiple daily dosing of intravenous interferon (IFN) in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B. METHODS: IFN-beta was intravenously administered at a total dose of 102 million international units (MIU) over a period of 28 d in 26 patients positive for HBeAg and HBV-DNA. IFN-beta was administered at doses of 2 MIU and 1 MIU on d 1, 3 MIU twice daily from d 2 to d 7, and 1 MIU thrice daily from d 8 to d 28. Patients were followed up for 24 wk after the end of treatment. RESULTS: Six months after the end of the treatment, loss of HBV-DNA occurred in 13 (50.0%) of the 26 patients, loss of HBeAg in 9 (34.6%), development of anti-HBe in 10 (38.5%), HBeAg seroconversion in 8 (30.8%), and normalization of alanine aminotransferase (ALT) levels in 11 (42.0%). CONCLUSION: This 4-wk long IFN-beta therapy, which was much shorter than conventional therapy lasting 12 wk or even more than 1 year, produced therapeutic effects similar to those achieved by IFN-alpha or pegylated-IFN-alpha (peg-IFN). Fewer adverse effects, greater efficacy, and a shorter treatment period led to an improvement in patients' quality of life. IFN-beta is administered intravenously, whereas IFN-alpha is administered intramuscularly or subcutaneously. Because both interferons are known to bind to an identical receptor and exert antiviral effects through intracellular signal transduction, the excellent results of IFN-beta found in this study may be attributed to the multiple doses allowed by the intravenous route.