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
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
When I read a recent Hepatology editorial (Hepatology 2015; 61: 1106-8), I could not help think of the aforementioned title of this blog.
Here’s the scoop:
The two most commonly used medications for Wilson’s disease are trientine (Syprine) and D-penicillamine (Cupramine). For about 20 years, the original manufacturer of these medications kept the consumer cost at ~$1 per 250 mg tablet. Currently the cost of Syprine is ~$200 per 250 mg tablet and Cuprimine costs ~$55 per 250 mg tablet. This 200-fold increase translates into a yearly cost of ~$300,000.
How did this happen?
- Little competition
- Profit motive
- Patients are reluctant to protest (they need this medication to be manufactured)
Why is this outrageous?
This increase in cost was not driven by any new discovery or research innovation.
Are there options?
Zinc is inexpensive and may be an option after initial period of chelation/normalization of liver biochemistries. Zinc needs to be taken two to three times per day and “well away from meals for best absorption.”
Bottomline: These medication prices are outrageous.
- “Molecular pathophysiology of portal hypertension” Hepatology 2015; 61: 1406-15. Terrific review with excellent figures.
- “Ezetimibe for the treatment of Nonacloholic Steatohepatitis” (MOZART trial) Hepatology 2015; 61: 1239-50. This randomized double-blind, placebo-controlled trial with 50 patients (biopsy-proven NASH) showed that Ezetimbe was not significantly different from placebo in histologic response rates, serum aminotransferases, or in magnetic resonance elastography findings.
- Van Biervliet et al. “Clinical Zinc Deficiency as Early Presentation of Wilson Disease” JPGN 2015; 60: 457-9. Case report.
A recent publication (J Pediatr 2014; 165: 539-546) from the Childhood Liver Disease Research and Education Network (CHiLDREN) provides a strong rationale for close followup of biliary atresia (BA) patients with their native livers. The Biliary Atresia Study of Infants and Children (BASIC) is one of the ongoing longitudinal studies within CHiLDREN.
Among a cross-sectional study BASIC cohort of 219 children (median age 9.7 years) who survived with their native livers for at least 5 years, they had the following findings:
- In preceding 12 months, cholangitis occurred in 17%, and 62% had experienced cholangitis at least once following hepatoportoenterostomy (HPE) (also called Kasai procedure. The authors note wide discrepancy in usage of prophylactic antibiotics; some stop at 2 years following HPE and some never stop antibiotic prophylaxis.
- In preceding 12 months, bone fractures occurred in 5.5%. Overall, 15% had had at least one bone fracture at some point, which is higher than the general population. Only 14.6% of entire cohort were receiving vitamin D supplementation.
- Portal hypertension: clinically detectable splenomegaly, thrombocytopenia, ascites, and variceal hemorrhage were seen in 56%, 43%, 17%, and 9% of patients in this cohort.
- Health-related quality of life was reported as normal in 53%
- Mean height and weight z-scores were normal in this cohort.
- Over 98% had clinical or biochemical evidence of chronic liver disease.
Bottomline: This BASIC study shows the need for careful followup of “successful” biliary atresia patients and provides more accurate data regarding risks of specific complications.
Briefly noted: J Pediatr 2014; 165: 547-55. In this study with same first author (Vicky Ng), the investigators develop and validate a pediatric liver transplantation (LT) quality of live instrument for LT patients aged 8-18 years.
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A useful review of “pulmonary complications in chronic liver disease” (Hepatology 2014; 59: 1627-37) has been published.
The main topics included hepatopulmonary syndrome (HPS) , portopulmonary hypertension (POPH), and hepatic hydrothorax (HH).
A few of the key points:
HPS is most common of these conditions and is identified in 5-30% of cirrhosis patients. It is identified with abnormal oxygenation (screening with pulse ox <96%) due to intrapulmonary vascular dilatations. There is no established medical therapy. It is reversible with liver transplantation.
The hallmark of POPH is the development of pulmonary arterial hypertension associated with portal hypertension. It occurs in 5-10% of cirrhosis patients and often presents as dyspnea on exertion/fatigue. There are numerous pharmacologic treatments that may be useful, include the following:
- prostacyclin analogs like epoprostenol
- endothelin receptor antagonists like boesentan
- phosphodiesterase-5 inhibitors like sildenafil, vardenafil, and tadalafil
Severe POPH is a relative contraindication for liver transplantation.
HH is a transudative pleural effusion seen in 5-10% of cirrhosis patients. Initial management includes salt restriction and diuretics. Transjugular intrahepatic portosystemic shunt and thoracentesis are second-line options. Liver transplantation is curative.
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Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.
A consensus report on portal hypertension has helpful advice on a broad range of management issues and should be kept in mind as a handy reference (Pediatr Transplantation 2012; 16: 426-37). The report is concise and full of bullet points. It is based on a meeting of pediatric experts to modify adult guidelines (Baveno V) for pediatrics.
In many instances, the experts indicate that there is not enough pediatric data. Specific subjects include the following (along with some points):
- Treatment options for portal hypertension -consider screening for varices if thrombocytopenia and splenomegaly. ‘No indication to use beta-blockers to prevent varices.’
- Prevention of first bleeding episode -in the presence of varices (grade II or III), variceal ligation reasonable in selected children and/or within context of defined research protocols. Grade I varices can be flattened with insufflation, and grade III varices are confluent around circumference of esophagus (per Japanese Research Society for Portal HTN analysis)
- Role of hepatic venous pressure gradient measurement (HVPG) -‘panel was undecided as to whether HVPG measurements in children’ should be ‘part of specialized clinical practice or’ a research tool.
- Blood volume restitution -suggests use of platelets in cases of bleeding with profound thrombocytopenia (<20,000).
- Antibiotic prophylaxis -unclear whether empiric antibiotics in children are needed in the presence of variceal bleeding.
- Management of treatment failures -can retry endoscopy and if fails, consider transjugular intrahepatic portosystemic shunting (TIPS)
- Management of gastric varices -only case reports in children, thus no evidence-based recommendations.
- Prevention of rebleeding -variceal ligation (EVL) preferred in patients with cirrhosis. EVL should be performed every 2-4 weeks up to five sessions to eradicate varices after 1st bleed.
- Treatment of portal vein obstruction -diagnosis, natural history, anticoagulation, use of MesoRex bypass procedure, associated portal biliopathy -diagnosis and treatment. With regard to MesoRex, ‘controversy exists as to the appropriateness of ..this procedure in an asymptomatic child.’ Surveillance endoscopy may assist in decision-making.
- Hypersplenism with portal vein obstruction-in the presence of platelet count <50,000 and portal vein obstruction, strong consideration should be given to MesoRex procedure.
- Portopulmonary hypertension and hepatopulmonary syndrome -important to monitor oxygen saturation in patients with portal vein obstruction/other causes of portal hypertension. If <97%, additional investigation may be needed. Portopulmonary hypertension is best characterized with cardiac catheterization and hepatopulmonary syndrome with saline echocardiography.
- Other topics: Prevention of hepatic encephalopathy, managing bleeding episodes, endoscopic treatment
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As noted in previous post (Learning a lot from ChiLDREN (part 1) | gutsandgrowth), several recent studies highlight the benefits of multisite collaboration to study infrequent pediatric liver problems. In these studies, the Childhood Liver Disease Research and Education Network (ChiLDREN) has collected prospective longitudinal observational date from multiple centers; data from 10 centers provides useful information on the frequency of portal hypertension (PHT) in young adults with biliary atresia (BA) (JPGN 2012; 55: 57-73).
163 subjects were enrolled between May 2006 and December 2009. Seven patients were excluded due to the presence of polysplenia which interferes with the assessment of PHT.
Demographics: subjects ranged in age from 1 to 25 years with a mean of 9.2 years. 56% were female, 75% were caucasian.
PHT was considered definite if there was either a history of a PHT complication (variceal bleeding, ascites) or if there were clinical findings c/w PHT (both splenomegaly and thrombocytopenia). PHT was considered “possible” if either splenomegaly or thrombocytopenia was present and “absent” if no criteria were met.
- PHT: definite in 80 (49%), possible in 27 (17%) and absent in 56 (34%)
- 43 subjects had a history of PHT complications: 32 with esophageal variceal (EV) bleeding, 14 with ascites, and 8 with hepatopulmonary syndrome.
- Of the patients with EV, only 3 had normal platelet count and normal spleen size.
- One-third of subjects with EV bleeding survived with their native liver for at least 5 years.
- EV age of onset was highly variable; 7 had bleeding in the first two years of life.
- Growth parameters were fairly unremarkable in those with definite PHT.
- Long-term followup will be needed to identify factors which predict progression of PHT and the development of adverse outcomes.
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