Hepatobiliary tuberculosis in the developing world

Table 1 PRISMA-P search strategy

Item	Description
Identification	Record identified through database search (n = 132)	Sources: PubMed (n = 132)
Screening	Records after duplicates were removed (n = 115)
	Records screened (n = 115)	Records excluded (n = 77)
Eligibility	Full-text articles assessed for eligibility (n = 38)	Full-text articles excluded (n = 21); full text not found = 8; not hepatobiliary tuberculosis = 10; not a case report = 20; and individual patient data not available = 3
Included	Studies included in qualitative synthesis (n = 17)
	Studies included in quantitative synthesis (meta-analysis; n = 17)

Table 2 Summary of systematically reviewed clinical cases of hepatobiliary/miliary tuberculosis

Ref.	Country	Age (year)	Sex	Clinical presentation	Diagnostic modalities	Treatment	Outcome	Quality assessment
Patel et al[44], 2016	India	14	Female	Persistent, intermittent fever associated with chills, abdominal pain, anorexia for 1 mo; neurological symptoms	Ultrasound of abdomen with portosplenic doppler; CT scan of the abdomen; bacterial culture of liver abscess; TB-PCR; mycobacterium growth indicator tube culture; MRI of the brain	Dexamethaxone for meningitis; rifampicin, Isoniazid, pyrazinamide ethambutol	Neurological symptoms regressed; significant improvement	High
Sahin et al[45], 2014	Turkey			Elevated liver enzymes	Liver biopsy CT scan of the abdomen	Not specified	Not specified	Low
Diallo et al[46], 2016	Dakar, Sénégal	48	Female	Cholestatic jaundice, right upper quadrant pain, fever (38.5 °C) and weak general condition, weight loss of 15 kg in 2 mo; on physical examination there was jaundice, fever, abdomen was soft, tenderness at the RUQ with hepatomegaly	Abdominal ultrasound; thoracoabdominal CT scan; liver biopsy	Rifampicin, isoniazid, pyrazinamide ethambutol; levofloxacin (included in the triple therapy for 10 d)	Good evolution: Clinical improvement, normalization of liver function tests	High
Ozin et al[47], 2010	Turkey	43	Female	Initially complained of malaise and itching, with elevate liver enzymes and bilirubin; diagnosis: Hepatobiliary tuberculosis	Hepatobiliary tree and pancrease ultrasound; ERCP; liver biopsy	Rifampicin, isoniazid, pyrazinamide ethambutol	Liver function tests were improved	High
Jain et al[48], 2017	India	50	Male	Jaundice since 10 d associated with significant loss of weight & appetite; diagnosis: Hepatobiliary tuberculosis	Liver ultrasound; CT scan of the abdomen; MRCP; and liver hepatectomy	Rifampicin, isoniazid, pyrazinamide ethambutol	Responded well	High
Chang et al[49], 2018	Taiwan	80	Male	Smear-positive, culture confirmed pulmonary TB, fever and chills after 1 wk of treatment; abdominal pain; diagnosed with cholecystolithiasis	Abdominal ultrasound; sputum AFB	Laparoscopic cholecystectomy; rifampicin, isoniazid, pyrazinamide ethambutol	ABE were not noted	High
Chang et al[49], 2018	Taiwan	50	Male	A male patient in his 50 s with comorbid, medically controlled DM and COPD was diagnosed with pulmonary TB based on a histology report of a transbronchial lung biopsy and a mycobacterial; culture of bronchial washing sample; diagnosed with acute cholecystitis	Abdominal ultrasound; CT scan of the abdomen	Rifampicin, isoniazid, pyrazinamide ethambutol	Improved	High
Chang et al[49], 2018	Taiwan	50	Male	Hypertension and COPD, irregular medical control, diagnosed with smear-positive, culture-confirmed pulmonary TB. Two weeks prior to the commencement of standard anti-TB treatment, he had pneumonia with respiratory failure and septic shock; multiple cholelithiasis was noted with dilated intrahepatic duct; treatment was halted	Hepatobiliary tree and pancrease ultrasound	Rifampicin, isoniazid, pyrazinamide ethambutol	Died of refractory septic shock	High
Chang et al[49], 2018	Taiwan	20	Male	Fever, chest pains, left pleural effusionImpression: Intermittent biliary obstruction due to a passing of stone	Sputum-AFB	Rifampicin, isoniazid, pyrazinamide ethambutol	Improved	High
Yamashita et al[50], 2014	Japan	48	Female	Past history of systemic lupus erythematosus developed autoimmune hepatitis, fever; diagnosis: Miliary tuberculosis	CT scan of the abdomen; liver biopsy	Isoniazid, rifampicin, ethambutol, pyrazinamide; subsequently changed to levofloxacin, ethambutol and streptomycin	Recovered liver function improved and no inflammatory reaction	Moderate
Yamane et al[51], 2010	Japan	47	Male	Incidental finding of an abnormality in the duodenum during endoscopy; no subjective symptoms; diagnosis: Tubercular papillitis of vater	Esophagogastroduodenoscopy; colonoscopy	Rifampicin, isoniazid, pyrazinamide ethambutol	Improvement of the duodenal lesion and colonic lesion	High
Ratanarapee et al[52], 1991	Thailand	38	Male	2-mo history of painless obstructive jaundice; cachectic and deeply icteric, with a normal temperature and an impalpable liver; diagnosis: Tuberculosis of the common bile duct	Ultrasound of the hepatibiliary tree	Rifampicin, isoniazid, ethambutol	Good health	High
Tewari et al[53], 2009	Japan	70	Female	Episodes of mild upper abdominal pain and vomiting of 3 mo; mild jaundice for 2 mo that subsided on its own; diagnosis: Tubercular ampullary papillitis	Ultrasound of the abdomen; CT scan of abdomen; EGD; ERCP; excision of the ampulla, with biopsy	Rifampicin, isoniazid, pyrazinamide ethambutol	Improved	High
Li et al[54], 2015	China	39	Female	10-d history of fatigue, anorexia, and jaundice. She had no abdominal pain or fever; diagnosis: Pelvic and Salpinx tuberculosis with secondary fulminant hepatic failure	CT scan of abdomen	Rifampicin, isoniazid, pyrazinamide ethambutol	Died as a consequence of ischemic cholangitis and pulmonary infection	High
Hickey et al[35], 1999	Ireland	50	Male	Pyrexia of unknown origin which was ongoing for 2.5 yr with multiple previous hospital admissions; diagnosis: Splenic tuberculosis	Ultrasound of the abdomen; abdominal CT scan	Rifampicin, isoniazid, pyrazinamide ethambutol	Well for over 6 yr	High
Hickey et al[35], 1999	Ireland	70	Male	6-wk history of progressive jaundice, severe pruritus, dark; urine, pale stools, and weight loss, with groin swelling	Percutaneous transhepatic cholangiography; biopsy of groin swelling	Rifampicin, isoniazid, pyrazinamide ethambutol	No recurrence for 5 yr	High
Gaspar et al[55], 2018	Portugal	35	Male	Fatigue, fever, weight loss, cough, abdominal pain, diarrhea, pruritus, hepatomegaly; diagnosis: Hepatic granuloma	CT scan of the abdomenliver biopsy	Rifampicin, isoniazid, pyrazinamide ethambutol	Discharged from the hospital	Mod
Musumba et al[56], 2013	United Kingdom	47	Male	5-d history of intermittent fever, rigors and night sweats; post cadaveric renal transplant 1 mo prior, and receives immunosuppressive therapy; diagnosis: Miliary tuberculosis	Whole body positron emission tomography/computed tomography; liver biopsy	Rifampicin, isoniazid, pyrazinamide ethambutol	Good clinical response	High
Poplin et al[57], 2020	United States	52	Male	1 mo PTC, hospitalized for culture-negative spontaneous bacterial peritonitis, liver disease was incidentally found; recurrent fever; diagnosis: Miliary TB; end-stage liver disease	Liver biopsy; CT scan of abdomen	Rifampicin, ethambutol, levofloxacin, amikacin 3 times weekly	Died due to ABE	High
Huang et al[21], 2003	Taiwan	47	Male	Epigastric pain; CT scan solitary liver nodule 13.5 cm tumor left lobe	Lobectomy, anti-TB Meds	Rifampicin, isoniazid, pyrazinamide ethambutol	Improved	High
Huang et al[21], 2003	Taiwan	57	Male	Malaise, weight loss; CT scan; solitary liver nodule 5.0 cm tumor at the left lobe	Wedge resection, anti-tb meds	Rifampicin, isoniazid, pyrazinamide ethambutol	Improved	High
Huang et al[21], 2003	Taiwan	63	Male	Managed for gastric cancer; CT scan; solitary liver nodule 2.0 cm at segment IV	Wedge biopsy		Expired	High
Huang et al[21], 2003	Taiwan	67	Female	Managed for gastric cancer; CT scan MULTIPLE small liver nodules at both lobes	Biopsy, refused treatment	Rifampicin, isoniazid, pyrazinamide ethambutol	Dropped out of management	High
Huang et al[21], 2003	Taiwan	71	Female	Epigastric pain with upper gastrointestinal tract bleeding; CT scan; solitary liver nodule 12.0 cm at the left lobe; nodular density at the right lower lung field on chest X-ray	Left hepatectomy; anti-tb meds	Rifampicin, isoniazid, pyrazinamide ethambutol	Improved	High
Zhang et al[29], 2014	China	30	Male	Weight loss, poor appetite, body weakness, abdominal distention, chest congestion	CT scan; FNAB	Rifampicin, isoniazid, pyrazinamide ethambutol	Improved	High

TB: Tuberculosis; COPD: Chronic obstructive pulmonary disease; FNAB: Fine needle aspiration biopsy; RUQ: Right upper quadrant; MRCP: Magnetic resonance cholangiopancreatography; ERCP: Endoscopic retrograde cholangiopancreatography; CT: Computed tomography; MRI: Magnetic resonance imaging; PCR: Polymerase chain reaction; ABE: Acute biliary events.

Table 3 Quality assessment of included cases of hepatobiliary and miliary tuberculosis

Ref.	Case number	Selection	Ascertainment		Causality				Reporting	Quality assessment
		Q1	Q2	Q3	Q4	Q5	Q6	Q7	Q8
		Did the patient(s) represent the whole case(s) of the medical center?	Was the exposure adequately ascertained?	Was the outcome adequately acertained?	Were other alternative causes that may explain the observation ruled out?	Was there a response to the specific treatment for tuberculosis?	Was there a histological confirmation of the diagnosis?	Was follow-up long enough for outcomes to occur?	Is the case(s) described with sufficient details to allow other investigators to replicate the research or to allow practitioners make inferences related to their own practice?
Patel et al[44], 2016	1	No	Yes	Yes	Yes	Yes	Yes	Yes	Yes	High
Patel et al[44], 2016	1	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	High
Sahin et al[45], 2014	35	Yes	Yes	Yes	Yes	No	Yes	No	No	Low
Diallo et al[46], 2016	1	No	Yes	Yes	Yes	Yes	Yes	Yes	Yes	High
Ozin et al[47], 2010	1	Yes	Yes	Yes	Yes	Yes	Yes	No	Yes	High
Jain et al[48], 2017	1	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	High
Chang et al[49], 2018	4	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	High
Yamashita et al[50], 2014	1	No	Yes	Yes	No	Yes	Yes	Yes	No	Low
Yamane et al[51], 2010	1	Yes	No	Yes	Yes	Yes	Yes	Yes	Yes	High
Ratanarapee et al[52], 1991	1	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	High
Tewari et al[53], 2009	1	Yes	Yes	Yes	Yes	Yes	Yes	No	Yes	High
Li et al[54], 2015	1	No	Yes	Yes	Yes	Yes	Yes	Yes	No	High
Hickey et al[35], 1999	2	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	High
Gaspar et al[55], 2018	12	Yes	No	Yes	Yes	No	Yes	No	Yes	Mod
Musumba et al[56], 2013	1	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	High
Poplin et al[57], 2020	1	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	High
Huang et al[21], 2003	5	Yes	No	Yes	Yes	Yes	Yes	Yes	Yes	High
Zhang et al[29], 2014	1	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	High