As a hepatologist practicing in a busy liver center in the Western United States, most of my encounters with hepatolithiasis have been in immigrated Asian patients. Hepatolithiasis is infrequently seen in Western Europeans and North Americans. Therefore, we need guidance in caring for these patients. Who do we observe? In whom do we intervene? And which intervention is appropriate: operative or nonoperative? Most of the lessons we have learned about this disorder have come from Japan and other Asian countries. Most of the terminology and details of surgical and nonsurgical management of hepatolithiasis have been developed in the Far East (especially Taiwan and Japan).
In the late 1970s and early 1980s, some large retrospective reviews of hepatolithiasis from four countries (Japan, Taiwan, Hong Kong, and Singapore) defined the natural history of the disease. 1–3 Roughly 10% of patients who have gallstone disease in these countries have intrahepatic calculi. For reasons that are unknown, the intrahepatic calculi occur far more commonly in the left biliary system than in the right. The prevalence of the disorder appears to be different among different geographic areas within countries, as well as between the countries themselves. The age distribution varies as well. For instance, the disease is prominent in very young patients between ages 10 to 30 years in Taiwan, where one third of patients have the onset of symptoms before the age of 20 years. 2 On the other hand, in Japan, the disease appears to be more prominent in an older population, aged between 30 to 70 years. 1 Many synonyms for this disease have evolved over time, including pyogenic cholangitis, Chinese biliary obstructive syndrome, Japanese cholangitis, and oriental cholangiohepatitis.
More is known about the intrahepatic stones themselves than their cause. Unlike cholesterol stones, which are most prevalent in Western patients with biliary disease, calcium bilirubinate stones predominate in virtually all cases of intrahepatic calculi. 1 Because of the observation that the disease was most prevalent in rural and poverty-stricken areas of Asia, it was initially thought to be associated with parasitic infection of the biliary tract. As far as 20 years ago, it was recognized that Clonorchis sinensis was not likely to cause hepatolithiasis, as the parasite is rarely seen in Taiwan where up to 50% of patients with gallstone disease have intrahepatic calculi. 3 Also, Ascaris lumbricoides is no longer a prevalent infection in Japan where hepatolithiasis still persists, suggesting the past association with this parasite is probably incidental rather than causative. Overall, it appears as though the prevalence of the disorder is related more to the sensitivity of the imaging techniques used for detection than to the improving economy of these countries.
In the 1990s, it became clear from long-term morbidity and mortality data that hepatolithiasis could be a very serious and fatal condition. Most of the patients who underwent early stone removals had a high rate of recurrence that required repeat surgery. Up to 10% of patients died secondary to cholangitis, sepsis, secondary biliary cirrhosis, and the late development of cholangiocarcinoma. 4 Furthermore, it was observed that patients that underwent hepatectomy or who recovered from surgery without residual stones after choledochoscopy had a better prognosis. 4 Also, patients who underwent hepatectomy had a better quality of life, with a lower rate of recurrent stones, a lower mortality, and a decreased risk for development of biliary cirrhosis and cholangiocarcinoma. 4 The development of choledochoscopy permitted more careful postoperative observation of some patients and the nonsurgical management of others. Although these data suggested that hepatectomy and/or choledochoscopy are the keys to management, they are quite aggressive treatments for assymptomatic patients whose stones are discovered incidentally by imaging technique, a common situation in Western countries.
In this issue of the Journal, Kusano et al. 5 have added to our understanding of the natural history of untreated hepatolithiasis. The authors have followed a large number of patients with hepatolithiasis during a 15-year period, with a mean of more than 10 years. They focused on 122 of 311 patients who had no initial clinical signs of disease and who were diagnosed primarily by imaging techniques. Of these patients, 11.5% developed symptoms within 9 months to 7.5 years, with a mean of 3.5 years. Most of these were caused by stone migration from intrahepatic ducts to common bile ducts. Many of these patients showed lobar atrophy on computed tomographic (CT) scan as well, which is likely caused by chronic cholestasis. Only a minority of patients without symptoms (13%) showed lobar atrophy on CT scan, making this a potentially differentiating factor in a decision analysis for treatment.
The authors advocated hepatic resection in all patients who develop lobar atrophy regardless of symptoms because 2 of their 14 assymptomatic individuals with lobar atrophy developed cholangiocarcinoma. On the other hand, close observation without surgery or nonsurgical intervention appears to be appropriate for a great majority of patients who are asymptomatic and who do not have lobar atrophy. Because many of their symptomatic patients refused intervention, the authors were able to determine that the outcome of untreated hepatolithiasis in this group is usually quite poor, resulting in secondary biliary cirrhosis, cholangiocarcinoma, and death caused by one of these conditions.
Although, Kusano's article answers a number of questions for those of us who see assymptomatic patients with hepatolithiasis, many management issues remain unanswered. The authors pointed out that CT scan appeared to be the best diagnostic test, but they did not comment on magnetic resonance image scanning, CT cholangiography, or the advent of magnetic resonance cholangiography. Would these modalities be better than CT scanning? Is dual-phase contrast CT scanning best and how frequently should scanning be performed? Annually or more frequently? Would liver biopsy be valuable in determining the development and progression of biliary fibrosis?
It is clear from the authors' careful review that the majority of patients with hepatolithiasis are assymptomatic patients that have no lobar atrophy on CT scan and who do not have common bile duct stones. It is quite possible that many of these patients will remain symptom-free throughout their lives and may be spared complex, costly, and potentially hazardous biliary tract interventions or hepatectomy. I think one may safely make some simple conclusions regarding the management of hepatolithiasis:
- Many patients are asymptomatic and may be watched with some imaging modality (probably magnetic resonance cholangiography will be the best);
- Those with symptomatic disease need to be treated, either surgically or nonsurgically depending on the anatomy and stone burden;
- Those with localized lobar atrophy should undergo resection; and
- Those with advanced biliary cirrhosis should undergo transplant evaluation if no contraindications exist.
1. Nakayama F, Furusawa T, Nakama T. Hepatolithiasis in Japan: present status. Am J Surg 1980; 139: 216–20.
2. Chang T-M, Passaro E. Intrahepatic stones: the Taiwan experience. Am J Surg 1983; 146: 241–4.
3. Nakayama F, Soloway RD, Nakama T, et al. Hepatolithiasis in East Asia. Dig Dis Sci 1986; 31: 21–6.
4. Jan Y-Y, Chen M-F, Wang C-S, et al. Surgical treatment of hepatolithiasis: long-term results. Surgery 1996; 120: 509–14.
5. Kusano T, Isa T, Ohtsubo M, et al. Natural progression of untreated hepatolithiasis that shows no clinical signs at its initial presentation. J Clin Gastroenterol 2001; 33: 114–7.