Hepatolithiasis

Hepatolithiasis is the formation of biliary stones within the intrahepatic bile ducts. It is endemic in East and Southeast Asia but rare in Western countries. Hepatolithiasis typically affects individuals aged 30–70 years; prevalence is higher in women. The etiology is complex, involving a cycle of cholestasis, biliary infection, and stricture formation, with risk factors including anatomical abnormalities, infections, and metabolic factors. Symptoms include abdominal pain, fever, and jaundice, but many patients are asymptomatic. Diagnosis primarily involves imaging: Abdominal ultrasound is the initial modality and MRCP provides more detailed findings. Management for symptomatic patients is multidisciplinary and aims to remove stones, resolve strictures, and prevent complications such as recurrent acute cholangitis, liver abscess, secondary sclerosing cholangitis, and intrahepatic cholangiocarcinoma. Treatment options range from endoscopic procedures and lithotripsy to surgical interventions such as hepatectomy and, in severe cases, liver transplantation. The prognosis is worsened by advanced age, prolonged jaundice, and the development of cirrhosis or cholangiocarcinoma.

• Endemic in East and Southeast Asia, with a prevalence as high as 30% ^[1]
• Rare in Western countries ^[1]
• Typically occurs between 30–70 years of age, with peak incidence between 40–60 years of age ^[2]
• ♀ > ♂ ^[1]

Epidemiological data refers to the US, unless otherwise specified.

Risk factors ^[1][2]

• Bile duct abnormalities (e.g., Caroli disease, primary sclerosing cholangitis)
• Postsurgical biliary strictures
• Sphincter of Oddi dysfunction
• Infection
  • Biliary dysbiosis
  • Parasitic infections (e.g., Ascaris, Clonorchis sinensis, Opisthorchis viverrini, Schistosoma)
• Metabolic and genetic factors
  • Mutations in genes associated with bile production (e.g., ABCB4, ABCB11)
  • Cystic fibrosis
• Other factors, e.g.:
  • Low-protein and low-fat diets
  • Malnutrition
  • Low socioeconomic status

• May be asymptomatic^[1][3]
• Abdominal pain or discomfort ^[1][3]
• Fever ^[3]
• Jaundice ^[3]
• Nausea and vomiting ^[1]
• Hepatomegaly ^[1]
• Charcot triad for cholangitis^[1]
• Reynolds pentad (severe cases) ^[1][2]

General principles ^[1][3]

• The diagnosis is primarily based on imaging studies.
• Laboratory studies support the diagnosis, but are nonspecific.
• Invasive testing (i.e., direct cholangiography, direct cholangioscopy, and bile duct cytology) is indicated to evaluate for intrahepatic cholangiocarcinoma if:
  • Patients are symptomatic.
  • Intrahepatic stones are not seen on cross-sectional imaging.

Imaging ^[1][3]

• Abdominal ultrasound: typically the initial study
• MRCP: more detailed assessment of biliary tree, strictures, and dilatations
• Computed tomography: for identifying biliary dilatations and abscesses

Laboratory studies ^[1][3]

• Diagnostics for cholestasis
• Liver function tests
• Inflammatory markers
• Tumor markers (i.e., CEA, CA19-9) should be measured to assess the risk of intrahepatic cholangiocarcinoma.

General principles ^[1][2][3]

• Multidisciplinary management is recommended for symptomatic or complicated disease.
• Treatment goals are stone removal, stricture resolution, and prevention of cholangitis and cholangiocarcinoma.
• Asymptomatic cases without cholangiocarcinoma, liver atrophy, or biliary strictures or dilatation are managed with expectant management with periodic cross-sectional imaging.
• Pharmacological treatment to dissolve stones is not routinely recommended.
• Symptomatic patients are managed with endoscopy, percutaneous treatments, or surgery, depending on severity and complications.

Endoscopic or percutaneous management ^[2]

• Lithotomy: direct removal of stones
  • Endoscopic or percutaneous lithotomy
  • Peroral cholangioscopic lithotomy
  • Percutaneous transhepatic cholangioscopic lithotomy
• Lithotripsy: used for large or difficult-to-access stones ^[4]
  • Laser lithotripsy
  • Electrohydraulic lithotripsy
  • Extracorporeal shock wave lithotripsy

Surgical management ^[1][2][3]

• Hepatectomy reduces stone recurrence and the risk of cholangiocarcinoma; indications include:
  • Unilobar disease (especially the left lobe)
  • Liver atrophy or severe fibrosis
  • Liver abscess
  • Multiple stones with marked biliary dilatation or stricture
  • Confirmed or suspected intrahepatic cholangiocarcinoma
  • Inadequate response to nonsurgical treatments
• Liver transplantation is an option for incurable, end-stage disease; indications include:
  • Secondary biliary cirrhosis (decompensated or with recurrent cholangitis)
  • Diffuse bilateral stones refractory to other treatments
  • End-stage decompensated cirrhosis
  • Intrahepatic cholangiocarcinoma
  • A history of multiple stone-related surgeries

• Recurrent acute cholangitis ^[1]
• Liver abscess ^[2]
• Secondary sclerosing cholangitis ^[1]
• Portal hypertension ^[1]
• Liver failure ^[1]
• Intrahepatic cholangiocarcinoma^[1]

We list the most important complications. The selection is not exhaustive.

• All-cause mortality rates are increased in hepatolithiasis. ^[2]
• Poor prognostic factors include: ^[2]
  • Advanced age at diagnosis
  • Jaundice lasting ≥ 1 week
  • Reynolds pentad
  • Intrahepatic cholangiocarcinoma
  • Cirrhosis

The 10-year survival rate decreases from > 90% to < 45% if cirrhosis and/or cholangiocarcinoma develops. ^[2]