"Salvage techniques" are the key to overcome difficult biliary cannulation in endoscopic retrograde cholangiopancreatography.

Although the efficacy and safety of salvage techniques for biliary cannulation in endoscopic retrograde cholangiopancreatography (ERCP) have been reported, few reports analyzed the choice of techniques and their clinical outcomes in large cohorts. This study aimed to evaluate the outcomes of biliary cannulation in patients with native papillae. We retrospectively identified 1021 patients who underwent initial ERCP from January 2013 to March 2020. We investigated background factors, treatment details, cannulation success rates, and adverse event rates. Then we analyzed a series of treatment processes, including salvage techniques such as double guidewire technique (DGT), needle knife pre-cutting (NKP), and transpancreatic pre-cut papillotomy (TPPP). The initial ERCP success rate using standard technique alone was 62.8%, which increased to 94.3% including salvage techniques. Salvage techniques were frequently required in patients with long oral protrusions (OR 2.38; 95% CI 1.80-3.15; p < 0.001). A total of 503 cases (49.3%) had long oral protrusions, 47.5% of which required the salvage techniques, much higher than 27.5% of not-long cases. Patients with long oral protrusions had a higher frequency of NKP. In conclusion, patients with long oral protrusions frequently required salvage techniques. Salvage techniques may help to overcome many difficult biliary cannulation cases.

Importance of computed tomography imaging features for the diagnosis of autoimmune acute liver failure.

AIM: The diagnosis of acute liver failure due to autoimmune hepatitis is often difficult because of atypical clinicopathological features. Patients with autoimmune acute liver failure are sometimes resistant to immunosuppressive therapy and have poor prognosis. Although their survival rates are especially poor (5-20%) without liver transplantation in Japan, their clinicopathological features have remained uncertain. A major problem is that there is no gold standard for making the diagnosis of acute onset autoimmune hepatitis. If there are diagnosing tools supporting clinicopathological features, they are of benefit to the patients. We examined computed tomography (CT) imaging features of autoimmune acute liver failure to clarify the usefulness of imaging for the diagnosis. METHODS: A retrospective analysis of 129 unenhanced CT scans of 68 patients with acute hepatitis, consisting of 23 with autoimmune acute liver failure (ALF) (group 1), 25 with early admission-viral ALF (group 2) and 20 with late admission-viral ALF (group 3), was performed. RESULTS: Autoimmune acute liver failure showed heterogeneous hypoattenuating areas and viral ALF diffuse ones (P < 0.001). The diffuse hypoattenuating areas were present in none of group 1, 15 (60%) of group 2, and 7 (30%) of group 3. The heterogeneous hypoattenuating areas were present in 15 (65%) of group 1, none of group 2 and 1 (5%) of group 3. CONCLUSIONS: Heterogeneous hypoattenuation on unenhanced CT was a characteristic CT imaging feature of autoimmune acute liver failure compared with viral ALF. This finding could be one of the tools for diagnosing autoimmune acute liver failure in combination with clinicopathological features.

Advanced histology and impaired liver regeneration are associated with disease severity in acute-onset autoimmune hepatitis.

AIMS: Some cases of acute-onset autoimmune hepatitis (AIH) develop into severe or fulminant forms showing massive/submassive hepatic necrosis, and have a poor prognosis. The pathological features of acute-onset AIH remain uncertain. Ductular (intermediate) hepatocytes after massive/submassive necrosis may serve as hepatic progenitor cells, and could be seen as cytokeratin 7 (CK7)-positive hepatocytes in immunohistochemistry. Therefore, the aim was to examine histological features to obtain a better evaluation of acute-onset AIH. METHODS: The histological features of 27 clinically acute-onset AIH patients were examined by immunohistochemistry using CK7. RESULTS: On staining for CK7, intermediate hepatocytes were less commonly present (P < 0.001) and ductular reactions were more commonly present (P < 0.001) in severe/fulminant patients than in non-severe ones. In severe and fulminant patients, intermediate hepatocytes and intralobular progenitor cells were more commonly present (P < 0.005 and P < 0.05, respectively) and ductular reactions were less commonly present (P = 0.007) in recovered patients than in dead ones. Severe patients had more clinically and histologically advanced disease. CONCLUSIONS: Immunohistochemical evaluation using CK7 might be a useful tool for evaluating liver regeneration, and intermediate hepatocytes and progenitor cells might play an important role in liver regeneration after massive and submassive necrosis in acute-onset AIH.

Autoimmune fulminant liver failure in adults: Experience in a Japanese center.

AIM: After the establishment of the international criteria of autoimmune hepatitis (AIH) in 1999 and the recognition of acute onset AIH, the diagnosis of patients with fulminant type of AIH came to be made. We diagnosed autoimmune fulminant liver failure based on the criteria, and discussed the etiology of fulminant hepatitis (FH) and late onset hepatic failure (LOHF), and the characteristics of autoimmune fulminant liver failure. METHODS: We investigated the etiology of 95 consecutive adult patients with FH or LOHF admitted to our liver unit between 1990 and 2009. Clinical and biochemical features, therapies and outcomes were examined in patients with AIH after 2000. RESULTS: Of 95 patients, 85 were FH and 10 LOHF. The etiology was due to viral infections in 51.6% (hepatitis A virus in 7.4%, hepatitis B virus in 43.2% and hepatitis E virus in 1.1%), AIH in 15.8%, drug allergy-induced in 12.6%, and unknown causes in 20.0%. The rate of patients with AIH increased significantly between 2000 and 2009 compared to the rate between 1990 and 1999 (P = 0.002). In recovered patients with AIH without transplantation after 2000, coma grade was lower, alanine aminotransferase level, prothrombin time activity and alfa-fetoprotein level were higher than in the others with statistical significance. CONCLUSION: AIH is not a rare cause of FH and LOHF, and the number of patients with unknown causes would surely decrease in concert with the precise diagnosis of AIH.

Hepatitis A viral load in relation to severity of the infection.

A correlation between hepatitis A virus (HAV) genomes and the clinical severity of hepatitis A has not been established. The viral load in sera of hepatitis A patients was examined to determine the possible association between hepatitis A severity and HAV replication. One hundred sixty-four serum samples from 91 Japanese patients with sporadic hepatitis A, comprising 11 patients with fulminant hepatitis, 10 with severe acute hepatitis, and 70 with self-limited acute hepatitis, were tested for HAV RNA. The sera included 83 serial samples from 20 patients. Viral load was measured by real-time RT-PCR. The detection rates of HAV RNA from fulminant, severe acute, and acute hepatitis were 10/11 (91%), 10/10 (100%), and 55/70 (79%), respectively. Mean values of HAV RNA at admission were 3.48 ± 1.30 logcopies/ml in fulminant, 4.19 ± 1.03 in severe acute, and 2.65 ± 1.64 in acute hepatitis. Patients with severe infection such as fulminant hepatitis and severe acute hepatitis had higher initial viral load than patients with less severe infection (P < 0.001). Viremia persisted for 14.2 ± 5.8 days in patients with severe infection and 21.4 ± 10.6 days in those with acute hepatitis after clinical onset (P = 0.19). HAV RNA was detectable quantitatively in the majority of the sera of hepatitis A cases during the early convalescent phase by real-time PCR. Higher initial viral replication was found in severely infected patients. An excessive host immune response might follow, reducing the viral load rapidly as a result of the destruction of large numbers of HAV-infected hepatocytes, and in turn severe disease might be induced.

The requirement for a sufficient period of corticosteroid treatment in combination with nucleoside analogue for severe acute exacerbation of chronic hepatitis B.

BACKGROUND: The prognosis of severe acute exacerbation of chronic hepatitis B is very poor if signs of liver failure appear. We have reported the efficacy of the early introduction of sufficient doses of corticosteroids (CSs) and nucleoside analogues (NAs), but the optimal period of immunosuppressive therapy has not been well demonstrated. In this study, we analyzed patients with severe acute exacerbation of chronic hepatitis B treated with CSs and NAs, prospectively, in order to clarify the factors affecting their outcome. METHODS: Ten patients, admitted to our liver unit between 2000 and 2009, were defined as having severe exacerbation of chronic hepatitis B based on our uniform criteria, and were enrolled in this study. NAs and sufficient doses of CS were introduced as soon as possible after making the diagnosis of severe disease prospectively. RESULTS: Seven of the 10 patients recovered. The absence of fulminant hepatitis on admission, the improvement of prothrombin time (PT) activity and the decline of hepatitis B virus (HBV) DNA during the first 2 and 4 weeks, respectively, were significant in the recovered patients, while the worsening of total bilirubin level during 4 weeks, especially between week 2 and week 4, was significant in those who died. CONCLUSIONS: In severe acute exacerbation of chronic hepatitis B, more than a few weeks of CS treatment in combination with an NA is required in the early stage, whereas a short period of conventional pulse therapy would be insufficient for treating this condition.