A survey (O Waisbourd-Zinman, et al. JPGN 2018; 66: 447-49) of 44 pediatric hepatologists (with 935 years of clinical practice) examined the issue of splenic rupture and spleen guards. ~90% of those surveyed reported following at least 30 patients with portal hypertension and splenomegaly.
- In total, the hepatologists could recall 13 cases of splenic rupture among patients with portal hypertension/splenomegaly due to cirrhosis –almost all of these occurred after a fall or in a motor vehicle accident. Only one of these falls happened during a sports-related event (soccer).
- 11 cases were serious. 9 of these cases resulted in shock with subsequent splenectomy, embolization, and/or death. Death reported in 2 cases.
- In this survey, 61% of hepatologists recommended “absolute restriction from activity with high risk of blunt abdominal trauma;” whereas 23% indicated that activities with risk of blunt trauma were acceptable if wearing a spleen guard.
- To prevent splenic rupture in patients with portal hypertension/splenomegaly, among the participating hepatologists, the majority identified the following ‘high risk’ sports: football (95%), hockey (82%), and wrestling (66%). A smaller percentage advocated a spleen guard for skiing (42%), soccer (41%), basketball (30%) and other sports.
While I did not participate in this survey, the one patient with chronic liver disease that I followed who had a splenic rupture had fallen down a flight of steps; fortunately, he recovered with supportive care.
My take: This survey shows that there is wide variability in the use of spleen guards. In almost all cases of splenic rupture, this was precipitated by severe trauma. Though, patients with portal hypertension may avoid high contact sports and thus the risks are for these sports is unclear.
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Foggy Morning in Sandy Springs
A concise and useful review of nonalcoholic steatohepatitis (NASH): AM Diehl, C Day. NEJM 2017; 377: 2063-72
A couple points:
- About 25% of adults have fatty livers in the absence of excessive alcohol consumption
- NASH is strongly associated with obesity/overweight which occur in >80% of patients
- NASH comorbidities in adults: 72% with dyslipidemia, 44% with type 2 diabetes mellitus
- In a typical patient with NASH, liver fibrosis progresses “at a rate of approximately one stage per decade, suggesting that F2 fibrosis will progress to cirrhosis within 20 years.” However, there is considerable variability.
- It is expected that NASH will be the leading reason for liver transplantation by 2020.
- Cirrhosis related to NASH increases the risk of hepatocellular carcinoma with this occuring in 1-2% per year of patients with cirrhosis.
- NASH is estimated to cost >$100 billion currently in annual direct medical costs
- Staging of NASH and differentiation from isoloated steatosis identifies those at high risk for sequelae.
- In Table 2, the authors list more than 10 pharmacologic agents in phase 2/3 studies
Current lifestyle treatment recommendations (for adults):
- Lose 7% of body weight if overweight or obese
- Limit consumption of fructose-enriched beverages
- Limit consumption of alcohol (no more than 1 drink/day for women and 2 drinks/day for men)
- Drink two or more cups of caffeinated coffee daily
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Panels A & B show typical histologic findings: ballooned hepatocytes (arrows), inflammatory infiltrates (arrowheads), and fibrosis Panel C shows the relative distribution of NASH, cirrhosis, and hepatocellular carcinoma in U.S. Adults.
There have been a number of studies suggesting a beneficial effect of statins for individuals chronic liver disease due to HBV infection, HCV infection, and nonalcoholic steatohepatitis. The potential reasons include lower portal hypertension due to increased nitric oxide availability, anti-inflammatory effects through reduction in some cytokines, and antifibrotic effects. In addition, statins may inhibit tumor initiation/hepatocellular carcinoma (HCC).
The background on these prior studies is detailed in a new population-based study (F-M Chang et al Hepatology 2017; 66: 896-907, editorial 697-9) of statins in patients with cirrhosis. In this nested case-control study from Taiwan, the authors examined patients (n=1350) with cirrhosis from 2000 to 2013. The index cases of cirrhosis were identified among a representative, well-validated general population database of 1,000,000 people.
- “Statin use decreased the risk of decompensation, mortality, and HCC in a dose-dependent manner.”
- Risk of decompensation among chronic HBV statin users, HR 0.39
- Risk of decompensation among chronic HCV statin users, HR 0.51
- Risk of decompensation among alcohol-related cirrhosis patients taking statins, HR 0.69
My take: In adults with cirrhosis, particularly HBV-related and HCV-related, taking a statin was associated with a 50-60% lower likelihood of decompensation. A prospective study could confirm these findings.
Prague -Charles Bridge
Briefly noted: The authors of a recent study (E Ceunen et al. Clin Gastroenterol Hepatol 2016; 14: 1552-58) set out to study whether it is likely that healthy adults could learn to fear “innocuous visceral sensations.” Fifty-two healthy subjects received 2 types of esophageal balloon distentions –one that was perceptible and non-painful and one that was painful. Not surprisingly, when the researchers paired these two interventions in the experimental group, the experimental group learned to fear the innocuous stimulation as well as the painful distention. This study provides theoretical support for one mechanism that could trigger ongoing functional gastrointestinal symptoms and a potential rationale for therapies, like cognitive behavioral therapy, which attempt to extinguish these symptoms.
In a retrospective study (AM Moon et al. Clin Gastroenterol 2016; 14: 1629-37) with 6451 patients with cirrhosis (mean age 60.6 yrs), the authors note that use of antibiotics during upper gastrointestinal bleeding (which is currently recommended) is associated with reduced mortality by ~30% at 30 days. Despite its benefit, this intervention is often overlooked. In the current study, only 48.6% of admissions received timely antibiotics; however, during the course of the study, the rate of antibiotic use improved from 30.6% in 2005 to 58.1% in 2013.
A recent retrospective study (N Goossens et al. Clin Gastroenterol 2016; 14: 1619-28) with 492 subjects showed that histologic NASH (in 12% of cohort) was associated with increased risk of death in patients who underwent bariatric surgery compared to patients without NASH. Overall, bariatric surgery reduced the risk of death during the study period with HR of 0.54; the median follow-up was 10.2 years, with surgery taking place 1997-2004. However, in patients with NASH the HR 0.90 which indicated that there was not a significant reduction in the risk of death.
Bar Harbor, ME (low tide)
A recent study (M Merli et al. Hepatology 2016; 1632-39) indicates that health-care associated infections (HCA) in the setting of cirrhosis respond more favorably to broad-spectrum antibiotics. In this prospective study of 96 randomized patients, in-hospital mortality was improved in the broad-spectrum group (6%) compared to the standard group (25%). There was a similar multidrug-resistnace rate (50% broad spectrum compared with 60% in standard group).
Table 1 lists the antibiotic selection. In the broad spectrum treatment, this almost always included imipenem/cilastin (I/C); with spontaneous bacterial peritonitis (SBP), I/C was combined with vancomycin, and with pneumonia it was combined with both vancomycin and azithromycin. In contrast, the standard group’s main medication was augmentin (with added azithromycin for pneumonia) or cefotaxime for SBP.
My take: Does this study show that infections in the setting of cirrhosis are becoming more difficult to treat? Probably. How much these findings can be extended to the pediatric population remains uncertain.
Somewhat related topic: Primary prophylaxis of Variceal Bleeding in Children –Summary of the Baveno VI Pediatric Satellite Symposium. BL Shneider et al. Hepatology 2016; 63: 1368-80. Key point: “there are few pediatric data…therefore, no recommendations for primary prophylaxis with endoscopic variceal ligation, sclerotherapy, or nonspecific beta-blockade in children was proposed.”
Silver Comet Trail
Before the recent vast improvements in hepatitis C virus (HCV) treatment, there had been a number of studies predicting a huge increase in HCV-related mortality due to hepatocellular carcinoma (HCC) and cirrhosis.
Despite the optimism that have come with the new treatments, the most recent data (LA Beste, et al. Gastroenterol 2015; 149: 1471-82) continue to predict a huge and increasing burden of chronic liver disease due to HCV.
The authors used a national retrospective cohort of Veteran Affairs (VA) patients with cirrhosis (n=129,998) or HCC (n=21,326) from 2001-13. They identified an increasing proportion of cirrhosis and HCC during that timeframe.
- From 2001 to 2013, cirrhosis prevalence nearly doubled (664 –>1058 per 100,000 enrollees) driven by HCV and nonalcoholic fatty liver disease; deaths due to cirrhosis also increased from 83 to 126 per 100,000 patient years
- From 2001 to 2013, HCC incidence increased 2.5-fold from 17 to 45 per 100,000 patient-years and HCC mortality tripled from 13 to 37 per 100,000 patient-years. HCC incidence was driven overwhelmingly by HCV.
- Based on current trends, cirrhosis prevalence will peak in 2021 according to the authors, though they acknowledge that patients from the VA may not be representative of the population at large and that the study has inherent weaknesses due to computerized data collection in this retrospective study.
My take: Despite dramatic improvements in HCV treatment, sadly, it is still going to get a lot worse with regard to disease burden & mortality from HCV before it will improve.
Briefly noted: F Negro. Gastroenterol 2015; 149: 1345-60. “Extrahepatic morbidity and mortality of chronic hepatitis C” This review article discusses diabetes, cardiovascular manifestations of HCV, fatigue, cognitive impairment, mixed cryoglobulinemia, and non-hodgkin lymphoma.
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A recent report (BK Burton et al. NEJM 2015; 373: 1010-20, editorial 1071-1) provides preliminary evidence of efficacy of Sebeliplase Alfa for lysosomal acid lipase deficiency.
In this multicenter, randomized, double-blind, placebo-controlled study of 66 patients, enzyme replacement therapy with Sebelipase alfa was examined (1 mg intravenously every other week). After 20 weeks, all patients were treated by open-label. Of the 32 patients who had had liver biopsies, 10 (31%) were noted to have cirrhosis.
- Alanine aminotransferase normalized in 11 (36%) of treated patients compared with 2 (7%) of controls
- Improvement in lipid levels and reduction in hepatic fat content were evident in treated patients (P<0.001 for all comparisons, except P-0.04 for triglycerides
The editorial provides a schematic explaining how sebelipase alfa targets the hepatocyte (Figure 1). The authors note that “longer-term follow-up in a larger number of patients will be required for confirmation.”
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