Cholangiocarcinoma: Has there been any progress?

Cholangiocarcinoma is the second most common primary hepatic tumour after hepatocellular carcinoma. Primary sclerosing cholangitis is one of the most commonly recognized risk factors for cholangiocarcinoma; however, approximately 90% of patients have no identifiable risk factors. Extrahepatic type is its most common presentation. Cholangiocarcinoma is considered to be a devastating disease, with a poor survival rate and few therapeutic options. Although surgical resection has been considered the best treatment option for localized cholangiocarcinoma, local recurrences of this cancer are very common, and imply persistent micrometastatic disease in lymph nodes or at surgical margins, even after extended surgical resection. Consequently, the five-year survival rate after attempted curative resection is only 20% to 40%. Early studies of liver transplantation for cholangiocarcinoma did not show a survival benefit and, currently, this tumour is considered to be an absolute contraindication for liver transplantation in most transplant centres worldwide. Recently, neoadjuvant chemoradiation in combination with liver transplantation for highly selected patients with cholangiocarcinoma has shown impressive results, with five-year survival rates at approximately 76% to 82% – similar to other standard indications for liver transplantation, such as hepatocellular carcinoma or hepatitis C-induced cirrhosis. However, this success of liver transplantation applies to only a subset of patients and most of the data originated from a single centre. Wider application of this strategy, especially for patients with potentially resectable disease, will require validation by other centres.     

Vitamin D Is Associated with Clinical Outcomes in Patients with Primary Biliary Cholangitis

Vitamin D (VD) deficiency has been associated with clinical outcomes in patients with chronic liver disease. This study aims to identify the prevalence of VD deficiency in patients with primary biliary cholangitis (PBC) and its association with treatment response to ursodeoxycholic acid (UDCA), cirrhosis development, and liver-related events (mortality and liver transplantation). Two hundred and fifty-five patients with PBC diagnosis were evaluated. Patients with VD levels below 50 nmol/L were defined as deficient. Treatment response to UDCA was defined according to the Toronto criteria. Independent risk factors were identified using binary logistic and Cox regression analysis. The mean level of serum VD was 77 ± 39 nmol/L, and 64 patients (25%) were VD deficient. Incomplete response to UDCA was more prevalent in VD-deficient patients compared to their counterparts (45% vs. 22%; p < 0.001). The risk of cirrhosis development (hazard ratio (HR) 1.93; 95% confidence interval (CI) 1.17–3.19, p = 0.01) and liver-related mortality or need for liver transplantation (HR 3.33, 95% CI, 1.57–7.07, p = 0.002) was higher in VD-deficient patients after adjusting for confounders. Vitamin D deficiency is frequent in patients with PBC and is associated with incomplete response to UDCA, cirrhosis development, and liver-related mortality or need for liver transplantation.     

Performance of the international classifications criteria for autoimmune hepatitis diagnosis in Mexican patients

The revised score of the International Autoimmune Hepatitis Group (R-IAIHG) and the simplified criteria (SC) are used for diagnosis of autoimmune hepatitis (AIH). Our aim is to evaluate the performance of these classifications to differentiate AIH from other autoimmune liver diseases. The frequency of diagnosis of definite AIH was similar both by the R-IAIHG and the SC systems (41% versus 40%), whereas diagnosis of probable AIH was made more commonly by the R-IAIHG than the SC (59% versus 29%), and 23 patients that have been graded as definite (n?=?7) or probable (n?=?16) AIH by the R-IAIHG had non-diagnostic scores by the SC system. The scoring systems rendered concordant diagnosis of definite (n?=?15) and probable (n?=?13) AIH in 28/73 patients (38%). Discordant diagnoses of AIH were rendered in 45/73 patients (62%). The R-IAIHG exhibited a sensitivity of 95%, specificity of 90%, and positive predictive value (PPV) and negative predictive value (NPV) of 93% for both. On the other hand, the SC had a lower sensitivity (65%) but a higher specificity (100%), PPV of 100%, and NPV of 68%. In conclusion, both international scoring systems diagnosed the same number of cases as definite AIH. The R-IAIHG showed a higher sensitivity in diagnosing AIH, whereas the SC showed a higher specificity. SC are easier to apply at the bedside and exclude more patients that could have a different etiology.     

Improving the end point of corticosteroid therapy in type 1 autoimmune hepatitis to reduce the frequency of relapse

OBJECTIVE: Relapse of autoimmune hepatitis may reflect incomplete suppression of disease activity prior to corticosteroid withdrawal, and liver tissue examination prior to the termination of therapy may be insufficient to predict subsequent course. Our goal was to refine treatment end point criteria so as to reduce the frequency of relapse after drug withdrawal. METHODS: One hundred thirty-two patients with definite type 1 autoimmune hepatitis who fulfilled clinical, laboratory, and histological criteria for remission were evaluated. The degree of laboratory improvement at the termination of treatment was correlated with subsequent clinical course in patients who had improved to normal or near-normal histological findings during corticosteroid therapy. RESULTS: Serum aspartate aminotransferase (AST) levels at the end of treatment were higher in patients who subsequently relapsed than in those who sustained remission (32 +/- 2 U/L vs 25 +/- 2 U/L, P= 0.04). Serum gamma-globulin (1.4 +/- 0.1 g/dL vs 1.2 +/- 0.1 g/dL, P=0.03) and immunoglobulin G (IgG) (1,416 +/- 55 mg/dL vs 1,079 +/- 57 mg/dL, P=0.001) levels were also higher in these patients prior to termination of therapy. The frequencies of abnormal serum AST (40%vs 13%, P=0.008), gamma-globulin (25%vs 3%, P=0.009), and IgG levels (36%vs 4%, P=0.001) at treatment withdrawal were also greater in the patients who subsequently relapsed. CONCLUSIONS: Patients who are treated to normal serum AST, gamma-globulin, and IgG levels have a lower frequency of relapse than others despite comparable histological findings.     

Patient and Caregiver Attitudes and Practices of Exercise in Candidates Listed for Liver Transplantation

Background

Impaired physical capacity increases peri-liver transplant complications. Patient perceptions regarding exercise prior to transplantation are not known.

Aims

This study aimed to assess patient and caregiver activity levels, perceptions of willingness to exercise, and of provider advice.

Methods

Consecutive patients listed for liver transplant and caregivers presenting for routine outpatient visits were evaluated over a 3-month interval. Anonymous surveys adapted to patients and caregivers addressed the importance and safety of exercise, type and duration of exercise performed, barriers, willingness to wear a monitoring device, and perceived provider recommendations. Responses were logged on a Likert scale from 1 to 5.

Results

Three hundred and sixty-eight responses were received. Most participants perceived exercise as important. Patients exercised three times per week for 30 min. Eighty percent endorsed walking (median response: 2—agree; IQR 1–2). Most did not jog, swim, cycle, or strength train. Fatigue, reported by 70%, was the major barrier (2, IQR 1–3). Over 90% of caregivers endorsed exercise as important (1—strongly agree, IQR 1–2) and encouraged exercise (median response 2, IQR 1–2). Over 60% of patients (median response 2, IQR 1–3) and caregivers (median response 2, IQR 2–3) felt providers encouraged exercise.

Conclusions

Patients and caregivers are willing to exercise to optimize physical fitness prior to liver transplantation.

     

Frequency and significance of antibodies to cyclic citrullinated peptide in type 1 autoimmune hepatitis

OBJECTIVES: Determine the frequency, clinical phenotype, and prognostic implications of antibodies against cyclic citrullinated peptides in patients with type 1 autoimmune hepatitis. METHODS: Three hundred and ninety-five serum samples from 179 patients were tested by enzyme-linked immunosorbent assay, and findings correlated with clinical and histological features, frequency of HLA DR3 and DR4, and treatment outcome. RESULTS: Twenty patients (11%) had antibodies against cyclic citrullinated peptides. Seropositivity was associated with a higher frequency of rheumatoid arthritis (RA) (25 vs. 0%, P < 0.001). Patients with antibodies against cyclic citrullinated peptides also had a significantly greater occurrence of histological cirrhosis at presentation (47 vs. 20%, P = 0.01) and death from hepatic failure than seronegative patients (25 vs. 9%, P = 0.04). Cirrhosis at presentation occurred more commonly in the patients with antibodies against cyclic citrullinated peptides and RA than in the other patients (100 vs. 21%, P = 0.005). CONCLUSIONS: Antibodies against cyclic citrullinated peptides occur in a subgroup of patients with type 1 autoimmune hepatitis who have a greater occurrence of cirrhosis at presentation and death from hepatic failure. Their presence with RA at accession characterizes a subgroup with cirrhosis.     

Autoimmune liver diseases,hepatocellular carcinoma,and recurrence of autoimmunity post-liver transplantation

Liver transplantation for the autoimmune liver diseases (AILD), which includes autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclero...     

Sarcopenia Severity Based on Computed Tomography Image Analysis in Patients with Cirrhosis

Standardized sex-specific cut-offs for sarcopenia in cirrhosis are needed to identify the risk of clinical complications and to discriminate the severity of sarcopenia. We aimed to compare clinical characteristics between patients with cirrhosis categorized according to the severity of sarcopenia. Computed tomography images were taken at the 3rd lumbar vertebra from 603 patients with cirrhosis and 129 adult donors for living liver transplantation. Patients with skeletal muscle index (SMI) two standard deviations (SD) below the sex-specific mean value of young donors (18–40 years old) were categorized as having severe sarcopenia whereas patients with SMI between −1 and −2 SD of the sex-specific young adult mean values were categorized as having sarcopenia. In the cirrhosis group, 408 patients (68%) were male with the mean age of 57 ± 0.4 years, and MELD score of 14 ± 0.4. Patients were divided into three groups: severe-sarcopenic (SMI < 30 cm²/m² in females and <42 cm²/m² in males), sarcopenic (30 ≤ SMI < 37 cm²/m² in females and 42 ≤ SMI < 50 cm²/m² in males) and non-sarcopenic (SMI ≥ 37 cm²/m² in females and ≥50 cm²/m² in males). Patients with cirrhosis and severe sarcopenia had lower muscle radiodensity and higher plasma neutrophil as well as neutrophil to lymphocyte ratio levels than both non- and sarcopenic groups. The frequency of alcohol-induced cirrhosis, refractory ascites, hepatic encephalopathy, CRP > 20 mg/mL, and severe malnutrition was also higher in severe-sarcopenic patients. The interval between sarcopenia and severe sarcopenia may reflect a window of opportunity in which to intervene and mitigate muscle wasting to improve patient outcomes.