A Case of Hepatocellular Carcinoma Complicated by Fulminant Type 1 Diabetes Mellitus Shortly After Initiation of Durvalumab Plus Tremelimumab.

A 64-year-old man with cirrhosis was diagnosed with unresectable hepatocellular carcinoma and treated with a combination of durvalumab and tremelimumab. The patient had no history of diabetes mellitus. Three weeks later, the patient developed general fatigue, dry mouth, and polyuria.

Usefulness of atezolizumab plus bevacizumab as second-line therapy for patients with unresectable hepatocellular carcinoma.

Aim: To clarify the efficacy of atezolizumab (ATZ) plus bevacizumab (BEV) as the second-line therapy for patients with unresectable hepatocellular carcinoma (HCC).

Methods: The subjects were 82 patients with HCC receiving ATZ/BEV, including 33 patients with previous therapies with molecular-targeted agents (MTA). Therapeutic efficacy was evaluated using contrast-enhanced CT according to the mRECIST.

Switching from combination therapy with entecavir hydrate plus tenofovir alafenamide fumarate to tenofovir alafenamide fumarate monotherapy in patients with chronic hepatitis B based on nucleotide sequences of hepatitis B virus pregenome RNA.

Aim: Patients with chronic hepatitis B virus (HBV) infection experiencing viral breakthrough (BTH) or partial response (PR) during lamivudine (LAM) or entecavir hydrate (ETV) administration often took ETV plus tenofovir alafenamide fumarate (TAF) due to the emergence of a drug-resistance mutation. However, in patients lacking drug-resistance mutation against TAF, sufficient antiviral effects may be achievable with TAF monotherapy. We assessed the drug-resistance profile through nucleotide sequences of HBV pregenome RNA, and subsequently changed to TAF monotherapy from ETV plus TAF.

Significance of portal venous blood flow as a factor to determine liver function in patients with decompensated cirrhosis due to hepatitis C virus infection following achievement of sustained viral response by sofosbuvir plus velpatasvir.

Aim: To determine the outcomes concerning portal venous blood flow and portosystemic shunts in patients with decompensated cirrhosis due to hepatitis C virus (HCV) infection who achieved sustained viral response (SVR) following antiviral therapy.

Methods: Portal hypertension-related events and liver function were evaluated in 24 patients achieving SVR following sofosbuvir plus velpatasvir therapy.

Results: Serum albumin level (median; g/dL) increased from 2.

Long-term outcomes of patients with cirrhosis presenting with bleeding gastric varices.

Aim: To establish a therapeutic strategy for cirrhosis patients with gastric variceal bleeding.

Methods: The outcomes of 137 patients with bleeding gastric varices were evaluated.

Results: The bleeding source was gastroesophageal varices (GOV) in 86 patients, and gastric fundal varices (FV) in 51 patients.

Two Cases of Intraabdominal Bleeding Caused by Hepatocellular Carcinoma Rupture Soon after the Initiation of Chemotherapy with Lenvatinib.

We herein report two patients with hepatocellular carcinoma (HCC) who exhibited intraabdominal bleeding caused by tumor rupture soon after lenvatinib initiation. A hypervascular nodule was present in the lateral segment manifesting extrahepatic protrusion in an 81-year-old-man and in the caudate lobe, which was completely occupied by the tumor, in an 83-year-old-man. Both patients were given lenvatinib, and epigastralgia occurred suddenly three and five days later.

Superiority of tenofovir alafenamide fumarate over entecavir for serum HBsAg level reduction in patients with chronic HBV infection: A 144-week outcome study after switching of the nucleos(t)ide analog.

Background: To evaluate the long-term efficacy of switching of the nucleos(t)ide analog used for treatment from entecavir (ETV) to tenofovir alafenamide fumarate (TAF) in patients with chronic HBV infection.

Methods: A total of 103 patients with serum HBsAg levels of ≥100 IU/mL who had received ETV were enrolled. The nucleos(t)ide analog used for the treatment was switched from ETV to TAF, and the changes in serum HBsAg levels during the 144-week period before and after the drug switching were compared in 74 patients who had received ETV at least for 192 weeks.

Significance of furosemide in patients with cirrhosis treated with or without zinc acetate hydrate supplementation.

Background: The Japanese guidelines for the treatment of cirrhosis suggest zinc supplementation to prevent hepatic encephalopathy in patients with cirrhosis and zinc deficiency, although the factors that are associated with therapeutic efficacy remain unknown.

Method: A total of 159 patients with chronic liver diseases but without previous zinc supplementation were analyzed. Factors associated with serum zinc levels as well as the therapeutic efficacy of zinc supplementation were evaluated.

Furosemide as a factor to deteriorate therapeutic efficacy of tolvaptan in patients with decompensated cirrhosis.

Aim: To optimize the therapeutic strategy for patients with decompensated cirrhosis manifesting hepatic ascites and/or edema, factors affecting the outcome of patients receiving tolvaptan were evaluated.

Methods: The subjects were 165 patients receiving tolvaptan including 116 patients (70%) also treated with furosemide. The therapeutic efficacy of tolvaptan was defined as "effective" when a body weight reduction of 1.

Furosemide as a factor to deteriorate therapeutic efficacy of rifaximin in patients with decompensated cirrhosis.

Aim: To optimize the therapeutic strategy for cirrhotic patients manifesting hepatic encephalopathy, factors affecting the outcome of patients receiving rifaximin were evaluated.

Methods: The subjects were 95 patients receiving rifaximin. Serum ammonia levels were measured serially during rifaximin treatment.

Therapeutic efficacy of lenvatinib for patients with unresectable hepatocellular carcinoma based on the middle-term outcome.

Aim: This study sought to clarify the usefulness of lenvatinib for patients with unresectable hepatocellular carcinoma (HCC).

Methods: The subjects were 69 patients with HCC receiving lenvatinib; the median age was 73 years, and 14 and 67 patients had been previously treated with regorafenib and/or sorafenib and therapies without molecular-targeted agents, respectively. Therapeutic efficacy was evaluated using contrast-enhanced CT images obtained 4-8 weeks after the start of lenvatinib and the middle-term outcome using Kaplan-Meier method.

Involvement of portosystemic shunts in impaired improvement of liver function after direct-acting antiviral therapies in cirrhotic patients with hepatitis C virus.

Aim: Factors responsible for impaired improvement of liver function despite sustained viral response after direct-acting antiviral agents therapies in cirrhotic patients with hepatitis C virus need to be elucidated.

Methods: Liver function and the extent of portosystemic shunting were evaluated for 79 patients with compensated cirrhosis, in whom sustained viral response had been achieved after direct-acting antiviral agents therapies for hepatitis C virus at least 3 years earlier.

Results: Portosystemic shunts were observed in 63 patients (80%).

Significance of switching of the nucleos(t)ide analog used to treat Japanese patients with chronic hepatitis B virus infection from entecavir to tenofovir alafenamide fumarate.

The significance of switching of the nucleos(t)ide analog used to treat patients with hepatitis B virus (HBV) from entecavir (ETV) to tenofovir alafenamide fumarate (TAF) is uncertain. The subjects of this study were 159 patients with HBV who received treatment with ETV followed by TAF. Among these patients, serial changes in the HBV marker levels were monitored in 92 patients in whom the serum HBsAg levels were ≥100 IU/mL during the 48-week period immediately before and after the switching.

A case of genotype-3b hepatitis C virus in which the whole genome was successfully analyzed using third-generation nanopore sequencing.

A 42-year-old Chinese man with chronic hepatitis C virus (HCV) infection visited our hospital for antiviral therapy. The subgenotype could not be determined using the HCV GENOTYPE Primer Kit (Institute of Immunology, Tokyo, Japan), which can identify genotype 3a HCV exclusively among genotype 3 HCV. Thus, the whole-genome sequence of HCV was analyzed using the MinION nanopore sequencer (Oxford Nanopore Technologies, Oxford, UK), a third-generation single-molecule sequencing platform.

NS5A-P32 deletion as a factor involved in virologic failure in patients receiving glecaprevir and pibrentasvir.

Background: This study sought to clarify the factors involved in virologic failure in patients with HCV receiving retreatment with glecaprevir/pibrentasvir (GLE/PIB) in real-world practice.

Methods: Forty-two patients who had previously received direct-acting antivirals (DAAs) therapies consisting of 35, 3, 3, and 1 patient(s) with genotype (GT)-1b, GT-2a, GT-2b, and GT-3b HCV, respectively, received GLE/PIB for 12 weeks. Resistance-associated substitutions (RASs) at baseline were evaluated, and the dynamics of NS5A-RASs were assessed by deep sequencing in patients showing virologic failure.

Balloon-occluded retrograde transvenous obliteration as a procedure to improve liver function in patients with decompensated cirrhosis.

Aim: Portosystemic shunts aggravate liver function by decreasing portal blood flow. The usefulness of balloon-occluded retrograde transvenous obliteration (B-RTO), a standardized therapeutic procedure for gastric fundal varices (GFV), for the improvement of liver function was evaluated in cirrhotic patients with or without varices.

Methods: The subjects were 161 patients with portosystemic shunts.

Serum asunaprevir concentrations showing correlation with the extent of liver fibrosis as a factor inducing liver injuries in patients with genotype-1b hepatitis C virus receiving daclatasvir plus asunaprevir therapy.

Aims: Liver injury can occur during antiviral therapies with direct-acting antivirals (DAAs), potentially necessitating discontinuation of the therapies, with consequent worsening of the sustained viral response (SVR) rates, in patients with hepatitis C virus (HCV). To clarify the mechanisms involved in serum transaminase level elevation, we performed a retrospective evaluation of the serum concentrations of daclatasvir and asunaprevir, both classified as DAAs, in patients receiving treatment with a combination of the two drugs.

Methods: Subjects were 278 Japanese patients with genotype-1b HCV who received daclatasvir plus asunaprevir therapy for more than 4 weeks.

Significance of NS5B Substitutions in Genotype 1b Hepatitis C Virus Evaluated by Bioinformatics Analysis.

To evaluate the effects of HCV NS5B amino acid substitutions on treatment outcome in Ledipasvir (LDV)/Sofosbuvir (SOF) for Japanese patients with genotype 1b HCV infection, NS5B sequences were examined in i) seven patients experiencing virologic failure after LDV/SOF in real-world practice, ii) 109 SOF-naïve patients, iii) 165 patients enrolled in Phase-3 LDV/SOF trial. A218S and C316N were detected in all patients with viral relapse; the percentages of these substitutions in SOF-naïve patients were 64.2% and 55.

A case of colonic varices complicated by alcoholic cirrhosis treated using balloon-occluded retrograde transvenous obliteration.

A 44-year-old man with cirrhosis arising from alcohol abuse manifested melena caused by the rupture of esophageal varices. He received endoscopic variceal ligation for the initial hemostasis, followed by endoscopic injection sclerotherapy as an additional consolidation therapy. A CT examination performed at the time of admission revealed collateral veins developing around the ascending colon, in which the feeding and draining vessels were identified as the superior mesenteric vein and the right testicular vein, respectively.

Retreatment with sofosbuvir/ledipasvir with or without lead-in interferon-β injections in patients infected with genotype 1b hepatitis C virus after unsuccessful daclatasvir/asunaprevir therapy.

Aim: To improve the therapeutic efficacy of sofosbuvir/ledipasvir (SOF/LDV) for the retreatment of patients after daclatasvir/asunaprevir (DCV/ASV), a customized therapy with or without lead-in interferon (IFN)-β injections was formulated according to the types of resistance-associated substitutions (RAS) in the non-structural protein (NS)5A region of genotype 1b hepatitis C virus (HCV).

Methods: Thirty-three patients failing prior DCV/ASV received SOF/LDV for 12 weeks. Patients with HCV carrying unfavorable NS5A-RAS and/or those previously treated with simeprevir were given lead-in IFN-β injections twice a day for 2 weeks; sequential changes in the NS5A-RAS during the injection period were evaluated using deep sequencing.

Chronic hepatitis caused by hepatitis C virus showing a discrepancy between serogroup and genotype because of intergenotypic 2b/1b recombination: A pitfall in antiviral therapy with direct-acting antivirals.

A 40-year-old male patient with virologic relapse after daclatasvir plus asunaprevir therapy for a serogroup 1 hepatitis C virus (HCV) infection visited our hospital for retreatment. Virologic examinations revealed that a genotype 2b HCV strain carrying both NS3-S122N / D168A and NA5A-R30Q / L31M / Q54H / Y93H mutations had relapsed. The patient received sofosbuvir plus ribavirin therapy, but virologic relapse occurred once again.

"Reversi-type virologic failure" involved in the development of non-structural protein 5A resistance-associated variants (RAVs) in patients with genotype 1b hepatitis C carrying no signature RAVs at baseline.

Aims: The therapeutic efficacy of daclatasvir/asunaprevir was inferior in patients with non-structural protein 5A (NS5A)-R30Q mutant hepatitis C virus strains at baseline, compared with those with wild-type strains, even though the half maximal effective concentration of NS5A inhibitors was lower in mutant strains than in wild-type strains. In these patients, R30Q and Y93H mutant strains, which are highly resistant to NS5A inhibitors, emerged at virologic failure. The mechanisms involved in such virologic failure were examined.

Sequential therapy consisting of glucocorticoid infusions followed by granulocyte-monocyte absorptive apheresis in patients with severe alcoholic hepatitis.

Background: Activated leukocytes infiltrating the liver contribute to the provocation of alcoholic hepatitis. Glucocorticoid induces the demargination of leukocytes from the hepatic sinusoids, whereas granulocyte-monocyte absorptive apheresis (GMA) removes leukocytes from the circulation. Thus, the usefulness of a sequential therapy consisting of glucocorticoid infusions followed by GMA was evaluated in patients with severe alcoholic hepatitis.