Since the advent of DAAs, the number of daily done liver biopsies (LB) had been considerably lessened (9). Additionally, the suggested high accuracy of the non-invasive measures had imposed a big query on the current significance of LB in liver disease diagnosis. Confidently, LB is never to be outdated, and there will be always a substantial role for histopathological examination in solving diagnostic dilemmas (8). In this unique study we had investigated the current diagnostic needs of LB after quitting interferon therapy which was mainly dependent on LB finding adoption of the new DAAs.
Drug induced liver injury (DILI) is one of the most common indications of LB as its diagnosis is mainly based on exclusion of all other etiologies of liver diseases which is practically impossible without the print of LB (10).
Accordingly, DILI had attained the highest number of cases that had performed LB and included in the current study (17.45%). The presence of combined hepatitis and cholestasis, eosinophilia, along with centrilobular necrosis are the most prominent features of DILI. However, a wide range of histopathological patterns had been identified in DILI cases according to the offending drug. Picture of acute hepatitis, acute liver failure, steatohepatitis, granulomatous hepatitis and eventually some cases develop chronic hepatitis leading to liver cirrhosis (11). Once cirrhosis had been developed the recognition of the primary pathology is significantly concealed. In a recent Egyptian study, non-steroidal anti-inflammatory (NSAID) drugs was reported as the first offending drug in DILI occurrence (10). Similarly, were the results of the current study, where NSAID represented about 20% of cases, with 8% for herbal preparations, and 5% each of amoxycillin clavulanic acid and halothane.
Unrecognized drugs also represent 5% of cases which is a threatening alarm for more social orientation of drug hazards along with more governmental censorship for limitation of over the counter drugs.
NAFLD is considered the evolving most common cause of liver diseases nowadays. In the current study NAFLD was the second prevalent indication of LB 42(12.75%). The global prevalence of NAFLD in the Middle East is high and affects about 31.8% of adult population (12). Based on the strong association between NAFLD and the metabolic syndrome a new nomination had been emerged to be metabolic associated fatty liver disease (MAFLD) (13). Hepatic steatosis more than 5% along with ballooning, lobular inflammation and even fibrosis are the main characteristics of NASH (14). Despite the availability of many non-invasive measures for evaluation of steatosis and specifically fibrosis, LB is still the most accurate distinguishing maneuver of NASH from NAFLD (15). In MAFLD, the linkage between liver fibrosis and cardiovascular risks is well identified denoting higher rates of morbidity and mortality (13). Accordingly, LB is still mandated in this area either as a diagnostic or a prognostic measure. In spite of the necessity of LB in NAFLD diagnosis in all international guidelines, the only obstacle prohibiting generalization of this concept is the patient’s refusal. More efforts should be wielded to delineate and eliminate all patients’ fairs and illusions about LB.
In the current study, chronic viral hepatitis infections were the fourth cause of performing LB (12.36%). Five cases with hepatitis C, 25 cases with hepatitis B virus infection and 4 cases with dual hepatitis B and C infection.
The unprecedented Egyptian campaign for treating HCV, was greatly appreciated all over the world. Since the emergence of direct acting antiviral drugs (DAAs) against HCV, the number of performed LBs had remarkably lessened. Unlike interferon therapy of HCV, DAAs had limited the reliance on LB as a prerequisite of treatment decisions (7). However, LB is still indicated in chronic HCV cases that showed poor sustained viral response in order to define a concomitant disease either iron overload, steatosis or granuloma that could resist the therapy.
In chronic active hepatitis B virus (HBV) infection, antiviral therapy can often be initiated without the need of LB. However, the difficulty in determining disease activity and fibrosis by serologic and biochemical data in chronic HBV makes LB an important tool in the management of a subset of patients (7). Demonstration of the degree of fibrosis and/or inflammation or associated concomitant disease in LB is a decisive factor for both treatment indications (16).
In patients who have HBV DNA 2,000 IU/ml and at least moderate fibrosis, treatment may be initiated even if ALT levels are normal (17). Moreover, the debatable queries about either to treat or not those with HBV chronic active infections could be partially resolved relying on histopathological examination of LB (18).
The treatment of dual HCV and HBV infections are challenging, as treating HCV with DAAs had been associated with increase of HBV-DNA levels in patients with positive HBsAg. In some cases, elevated ALT and even liver failure may develop in these conditions (19-20). Accordingly, LB might be of significance in determining the most prevailing infection and determining treatment priorities.
In our series AIH patients are representing about 13% % of the whole cohort. From our data, LB is the most trustworthy diagnostic measure of AIH included in all old and recent scoring systems of AIH recommended by international guidelines (21). Remission of AIH is considered in those who develop normalization of both serum transaminases and IgG (22). However, normalization of either of them mandates reliance on histopathological examination of LB to assure remission (21). LB should be performed also for immunosuppression resistant cases for the possibility of overlap syndrome (which was detected in 2.45% of cases in the current study). Recognition of the prevailing pathology in overlap syndrome could not be assured without LB. Nevertheless, progression to liver cirrhosis in those patients remains the obstacle masquerading the prime pathology (21).
In the current series biliary tract diseases especially biliary cholangitis (PSC, PBC) are considered important causes of liver disease. They represent 17.9% of liver biopsies in the National liver disease. Biliary diseases should be taken in consideration as an important cause of liver disease as prolonged biliary inflammation leads to many serious complications like cholangitis, biliary abscesses and liver cirrhosis which is a fast devastating incident in this context (23). Biliary cirrhosis is distinguished to have a hastier course rather than other liver pathologies, a fact mandating early diagnosis and rapid management (24). Unlike PBC, LB is not mandated for most of PSC cases as magnetic resonance cholangiography (MRCP) and or endoscopic retrograde cholangiography (ERCP) remains the most reliable diagnostic measure (25). Cases with small duct PSC or overlap syndromes with PSC were the only cases relying on LB results (26). While destruction of small bile ducts is the most pathognomonic histopathological feature of PBC, the presence of onion skin fibrosis is the devastating sign of PSC (27).
Granulomatous hepatitis is the most diagnostic feature of sarcoidosis representing 4% of the current study cases. Diagnosis of cases with hepatic sarcoidosis might be challenging for the non-specific presentations. LB might be the last resolution for this dilemma. Non caseating numerable unpaired granuloma and intrahepatic cholestasis were found to be the prevailing histological features of hepatic sarcoidosis (28). However, sometimes the distinction from early non-caseating TB granuloma is frustrating necessitating resorting to more distinctive special stains (28).
The need of LB for recognition of hepatic Schistosomiasis was reported in 4.72% of current study cases. Schistosomal non-cirrhotic portal hypertension was the most prevalent diagnostic need for LB with the characteristic hepatic granuloma (29). Thanks to the governmental efforts, the prevalence of hepatic schistosomiasis had been dramatically ameliorated in Egypt (30).
Long ago, LB is only needed for exclusion of other causes of liver disease rather than diagnosis of Wilson disease (WD). The required dried weight liver tissue for proper diagnosis of WD is a cumbersome against LB. the wide range of histopathological presentations might also be another con (31). In accord, LB was needed in only in 10 cases (3.63%) in this research that were with clinical and laboratory inconclusive data.
Despite rarity, liver might be the seat of non-hepatotropic viral infections. Sometimes LB might be the leading suggestive measure of non-hepatotropic viral infections while searching of cause of the liver injury in a puzzling case (32). Epstein-Barr Virus (EBV) had affected 6 cases while cytomegalovirus (CMV) had affected 4 cases of patients included in the current study. The presence of lobular disarray, nuclear inclusion bodies, micro-abscesses, and lobular lymphocytic infiltration are the main histopathological features suggestive of CMV in LB (32).
In EBV, portal tracts are massively intruded by atypical lymphocytes and plasma cells. Intra-sinusoidal lymphocytosis often has a characteristic “Indian-file” appearance (32).
Seven cases of Dubin-Johnson syndrome were reported in the current study. Surprisingly these cases might present up to fifties with unexplained conjugated hyperbilirubinemia and normal transaminases. Grossly the liver appeared black with the absence of anti-MRP2 on immunohistochemical staining of liver tissue (33).
Liver abscess is a rare indications for liver biopsy in our study and represents less than 2%. In Cryptogenic pyogenic liver abscess is present in 60%of cases whenever there is no obvious identifiable risk factor (34). Most pyogenic liver abscesses are located in the right lobe of the liver because of portal vein anatomy, more hepatic mass and dense bile canaliculi in this lobe (35). This is also prominent in our series as 5 of 6 liver abscesses were found to be located in the right lobe of the liver. The imaging of the liver plays a corner stone in helping detection of liver abscess. Abdominal ultrasound and CT scan can help in diagnosis of 50% of cases (36). Nevertheless, LB is requested only in cases of early hepatic masses before evident liquefaction along with atypical imaging criteria.
Solitary cases of latent congenital hepatic fibrosis, amyloidosis, hemochromatosis, hepatic amoebiasis, malaria, polyarteritis nodosa, myeloproliferative disease was also reported in the current series.
The imaging guided LB had limited the associated risks of this interventional theoretically invasive maneuver. Regarding LB complications in the current study, pain requiring analgesia was the main complain (25.18%). Major complications represented only less than 1.18% with no reported mortalities. Bleeding (0.7%), biliary leak (03%), sepsis (0.03%) and pneumothorax (0.3%) were reported without either surgical interventions or unfavorable outcomes. Similarly, Elsenberg and his colleagues, had denoted the occurrence of pain even mild discomfort following LB in 84% (37). Also, Kose et al had reported that post-LB pain requiring analgesia was present in 19.8% and major complications in 1.15%. Major complications in their study included pneumothorax in 0.17%, haemobilia in 0.08% and hematoma in 0.9%) and absence of other complications like abscess, bacteremia, organ perforation and death (38). Also, Govender et al reported serious complications in a rate of 1.7% in their series in the form of pneumothorax, symptomatic hematoma and pseudoaneurysm and no deaths (39). The mortality rate attributed to the procedure is estimated in one per 10 thousand biopsies and is usually secondary to bleeding; this is even lower when the biopsy is not performed for evaluation of liver tumors (40). The reported higher rates of safety had denied any claims of high-risk probabilities.
In the current study, the complete absence of what was known as intra-observer variations denoting the highly professional skillful pathology team, adding more reliability to the maneuver.